Meira made his IndyCar debut on 11 August 2002 with Team Menard at Kentucky Speedway after impressing in an open test for Panther Racing at Texas Motor Speedway. Within four starts, he claimed his first career pole at Texas Motor Speedway and finished third. In 2003, he made his Indianapolis 500 debut for Team Menard, finishing twelfth as a rookie, before a practice crash at Kentucky Speedway ended his season early with a wrist injury.
In 2004, Meira joined Rahal-Letterman Racing on a race-by-race deal after missing the opening two rounds, taking a second career pole at The Milwaukee Mile in July. He earned a full three-year contract with the team for 2005, backed by Johns Manville and Menards. That season he finished second to Dan Wheldon at the Indianapolis 500 and guided Rahal-Letterman to their best-ever final championship standing, placing seventh overall with seven top-five and eleven top-ten finishes. The loss of sponsorship funds for the 2006 season cost him the Rahal-Letterman seat.
With few alternatives, Meira accepted an offer from Panther Racing for 2006 despite the team having lost its primary sponsor Pennzoil and engine supplier Chevrolet. The owners sold cars and parts to keep the programme alive and signed a deal with Honda. Running the No. 4 car with a rotating roster of sponsors including Econova, Harrah's, and Lincoln Tech, Meira delivered a career-best fifth in the IndyCar championship, with seven top-five and twelve top-ten finishes despite not winning a race. He signed a three-year extension with Panther and in 2007 was joined by Delphi Corporation as primary sponsor.
In 2008, with the United States National Guard as the primary backer, Meira again finished second at the Indianapolis 500, this time chasing eventual winner Scott Dixon. He closed to within 0.4 seconds of Dixon before late-race traffic cost him the lead, setting his fastest lap on lap 195 of 200.
For 2009, Meira moved to A.J. Foyt Enterprises, driving the No. 14. During the 2009 Indianapolis 500, his car survived a dramatic pit-lane fire and he later broke two vertebrae in his lower back in a crash involving Raphael Matos on lap 174. He did not require surgery and was treated with a back brace, but missed the remainder of the season.
Meira returned in 2010, taking a third-place podium in his home race in Brazil in his first event back — his best result that year. He drove for A.J. Foyt Enterprises again in 2011, finishing fifteenth in the championship with a best of fifth at Toronto. He was among the drivers involved in the fifteen-car accident that killed Dan Wheldon at the 2011 IZOD IndyCar World Championship finale in Las Vegas. Without a ride for 2012, Meira left American racing. He attempted a comeback for the 2015 Indianapolis 500 but could not secure a seat.
Meira became engaged to his longtime girlfriend Adriana in March 2006 and married her at the Little White Wedding Chapel in Las Vegas on 22 March 2008. After retiring from American racing, he founded a self-storage facility business in Brazil and took over an advertising agency originally started by his father.
Meira's two Indianapolis 500 runner-up finishes rank among the most compelling near-misses in the modern era of the event. His ability to deliver strong results for under-resourced teams — most notably the fifth-place championship finish with a stripped-down Panther operation in 2006 — earned him respect throughout the IndyCar paddock.
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