The course was made up of three different circuit length variations. These included the 72.00 km (44.74 mi) Piccolo short/small circuit, the 108.0 km (67.1 mi) Medio medium circuit, and the full 148.821 km (92.473 mi) Grande circuit. Several versions of the track were used, starting with a single lap of a 148.82 km (92.47 mi) circuit from 1906โ1911 and 1931. From 1912 to 1914, a tour around the perimeter of Sicily was used, with a single lap of 975 km (606 mi), lengthened to 1,080 km (670 mi) from 1948 to 1950. The 148.82 km (92.47 mi) "Grande" circuit was then shortened twice, first to 108.00 km (67.11 mi), used from 1919โ1930, and then to the 72.00 km (44.74 mi) circuit used from 1932 to 1936 and 1951 to 1977. From 1951โ1958, the long coastal island tour variant was used for a separate event called the Giro di Sicilia.
The start and finish took place at Cerda. The counter-clockwise lap led from Caltavuturo and Collesano from an altitude over 600 metres (1,970 ft) down to sea level, where cars raced from Campofelice di Roccella on the Buonfornello straight along the coast. This straight was even longer than the Mulsanne Straight at the Circuit de la Sarthe in Le Mans. The longest version of the circuit went south through Caltavuturo, climbing uphill through Castellana, Sottana, Madonnuzza, and Miranti, twisting around mountains up to 1,100 metres (3,600 ft) at Geraci Siculo, dropping down 620 metres (2,030 ft) into Castelbuono, twisting around more mountains and passing through Isnello and Mongerrati, then rejoining the most recent version of the track at Collesano. The second version of the track also went south through Caltavuturo and took a shortcut starting right before Castellana to Collesano via Polizzi Generosa. A closed circuit called Favorita Park in Palermo was used from 1937-1940. All the roads used for all the variations of the circuits are still in use today. The Buonfornello straight became wider in the late 1960s due to the development of the Autostrade motorways.
The challenge of the Targa Florio was unprecedented in its difficulty. The driving experience of any of the course variants was unlike any other circuit in the world, other than perhaps that of the Nurburgring in Germany and the Snaefell Mountain Course on the Isle of Man. All variants had 18 to 23 corners per mile (11 to 14 corners per kilometer). The original Grande 146 km (91 mi) circuit had about 2,000 corners per lap, the 108 km (67 mi) Medio had about 1,300-1,400 corners per lap, and the final 72 km (45 mi) Piccolo circuit had about 800-900 corners per lap. Learning any of the Targa Florio courses was extremely difficult, requiring at least 60 laps to learn properly in public traffic. One lap of even the Piccolo course would take about an hour in a road car with little to no traffic. Finishing this punishing race required a very reliable car, as it was very hard on the gearbox, brakes, and suspension.
Race cars were started one by one every 15 seconds for a time trial, as a start from a full grid was not possible on the tight and twisty roads. Lap speeds at the Targa Florio never went higher than 130 km/h (80 mph). Helmut Marko set the lap record in 1972 in an Alfa Romeo 33TT3 at 33 min 41 s, averaging 128.253 km/h (79.693 mph). The fastest ever was Leo Kinnunen in 1970, lapping in the Porsche 908/3 at 128.571 km/h (79.890 mph) or 33 min 36 seconds flat. The lap record for the 148.82 km (92.47 mi) "Grande" circuit was 2 hours 3 min 54.8 seconds set by Achille Varzi in a Bugatti Type 51 at the 1931 race, at an average speed of 70.7 km/h (43.931 mph). The lap record for the 108.00 km (67.11 mi) "Medio" circuit was 1 hour 21 min 21.6 seconds set by Varzi in an Alfa Romeo P2 at the 1930 race, at an average speed of 79.642 km/h (49.487 mph).
In the late 1960s and early 1970s, race cars with up to 600 hp (450 kW) such as Nino Vaccarella's Ferrari 512S raced through small mountain villages with spectators close to the road. Due to safety concerns, especially by Helmut Marko, the last Targa Florio as a World Sportscar Championship race was run in 1973. It became impossible to retain its international status after a number of accidents, two of which were fatal. One incident involved privateer Charles Blyth crashing his Lancia Fulvia HF into a trailer at the end of the Buonfornello straight, killing him. Another saw an Italian driver crash his Alpine-Renault into spectators, killing one. Several other accidents during practice for the 1973 event injured seven spectators. The event was won by a Porsche 911 Carrera RSR as prototypes like Jacky Ickx's Ferrari suffered crashes or other troubles.
The Targa Florio's international demise was compounded by concerns about the organizers' ability to maintain the race on such a massive circuit, with insufficient marshals and spectators too close to the roads. The FIA mandated safety walls on all circuits holding FIA-mandated events from 1974 onwards, which was impossible and impracticable for the 44-mile (71 km) length of combined public roads. Brian Redman crashed his Porsche 908/03 during the 1971 event, and it took 45 minutes for medical help to reach him. The Targa Florio continued as a national event for some years, before a crash in 1977 where Gabriele Ciuti went off the road and crashed at the fast curves at the end of the Buonfornello straight after bodywork flew off his BMW-powered Osella prototype. This accident killed 2 spectators and seriously injured 5 others, effectively sealing the race's fate. After this accident, the race was forcibly taken over by local police and stopped on the 4th lap. Despite its inherent dangers, only 9 people, including spectators, died at the event over its 71-year and 61-race history, using a total of 6 circuit configurations. This is relatively small compared to other open road races like the Mille Miglia and Carrera Panamericana, likely due to the extremely slow and twisty mountain roads and average lap speeds never reaching even 80 mph (130 km/h).
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