© 2017 The Author(s). Background: Anterior cruciate ligament (ACL) injuries occur commonly in football. Recent work has reported ACL reconstruction (ACLR) as one of several orthopaedic procedures with unfavorable outcomes for professional athletes. The performance impact to defensive players after surgery has not been quantified. Purpose: To quantify the effect of ACLR on the performance of defensive players by comparing them to a cohort of matched controls as well as to measure the effect of ACLR on athletes' career length in the National Football League (NFL). Study Design: Case-control and cohort study; Level of evidence, 3. Methods: Thirty-eight NFL defensive players with a history of ACLR from 2006 to 2012 were identified. For each injured player, a matched control player was identified. Demographic and performance statistics were collected from the online NFL player database. Players who returned after ACLR (n = 23) were compared with players who did not return (n = 15) using t tests and chi-squared analyses. Similarly, players who returned after ACLR (n = 23) were compared with their matched controls with t tests and chi-squared analyses. Two-way repeated-measures analysis of variance was utilized to test for significant differences between performance before and after the season of the injury for the players in the ACLR group who returned (n = 23) and for their matched controls. Kaplan-Meier analysis was performed to test for differences in the rate of retirement between the groups. For all analyses, P values <.05 were considered significant. Results: Approximately 74% (28/38) of athletes who underwent ACLR returned to play at least 1 NFL game, and 61% (23/38) successfully returned to play at least half a season (ie, 8 games). Athletes in the ACLR group who returned retired from the NFL significantly sooner and more often after surgery than their matched controls. In the seasons leading up to their injury, athletes who successfully returned to play started a greater percentage of their games (81%) and made more solo tackles per game (3.44 ± 1.47) compared with athletes in the ACLR group who did not return to play (54% and 1.82 ± 1.17, respectively) and compared with healthy control players (52% and 1.77 ± 1.19, respectively). After the season of surgery, athletes in the ACLR group who returned to play decreased to 57% games started and 2.38 ± 1.24 solo tackles per game, while their matched controls suffered no significant decreases. Conclusion: Players who successfully returned were above-average NFL players before their injury but comparatively average after their return.