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Background: Knee injuries, including articular cartilage damage, are common in football players and are potentially career threatening. The rate of return to play (RTP) as well as the factors affecting return after arthroscopic chondroplasty of the knee is performed in National Football League (NFL) athletes are not known. Purpose: To determine the rate of return to regular season NFL competition after arthroscopic knee surgery including chondroplasty of articular cartilage lesions. In addition, identification of factors that influence successful return was investigated. Study Design: Case series; Level of evidence, 4. Methods: Athletes in the NFL who underwent arthroscopic chondroplasty at a single institution were identified. Retrospective chart review and review of the NFL online database were utilized to determine the rate of RTP and factors affecting an athlete’s ability to return. Chi-square and Student t tests were used to assess differences among players who were and were not able to RTP, and logistic regression was employed to determine a player's odds of return. Results: There were 52 patients (54 procedures) identified from the surgical database who met the inclusion criteria for the study operated on between August 1, 2001, and March 31, 2011. Of these players, 36 (67%) were able to return to regular season NFL game play at an average of 8.2 months, including 13 (24%) who were still active in the NFL. The average time to follow-up was 5.9 years, and all players were allowed at least 2 years of follow-up. There was no significant correlation of RTP to athlete age, lesion size, lesion location, position played, or round selected in the NFL draft. Players who underwent concomitant microfracture were 4.4 times less likely to return to the NFL than were those who did not undergo this procedure (95% CI, 1.3-15.5). Athletes who played more than 11.6 games per season were 4.7 times more likely to RTP than were those who played fewer games per season (95% CI, 1.4-16.6). Athletes who returned to play competed in 56 fewer games, 3.3 fewer seasons, and played in 3.2 fewer games per season compared with their level of competition before surgery. Conclusion: A majority (67%) of NFL players are able to RTP after arthroscopic knee surgery including chondroplasty of articular cartilage lesions. Athletes who play more games per season are more likely to RTP after chondroplasty of articular cartilage lesions of the knee, but those undergoing concomitant microfracture are less likely to return. No statistical significance was determined when comparing the athletes who returned to play with respect to age at surgery, lesion location, lesion size, lesion grade, position that the athlete played, or draft round. [ABSTRACT FROM AUTHOR]