BACKGROUND::Anterior cruciate ligament (ACL) injury has been a major cause of missed game time among Australian Football League (AFL) players. Return to play after ACL reconstruction is not always achieved, even among elite athletes. The rate of subsequent ACL injury in the AFL from 1990 to 2000 was high as compared with that of other elite sports. PURPOSE::To determine the rates of return to play and subsequent ACL injury after ACL reconstruction among AFL players from 1999 to 2013 and to explore factors associated with differing rates of return to play and subsequent ACL injury. STUDY DESIGN::Case series; Level of evidence, 4. METHODS::A total of 158 AFL players who underwent ACL reconstruction were identified from a prospectively maintained registry of AFL player injuries. Further data were gathered from official playing statistics, surgical records, and structured phone interviews. RESULTS::The rate of return to play after an initial ACL injury was 77% (121 of 158 players). Greater preinjury playing experience and earlier selection in the AFL draft were associated with higher rates of return to play. The rate of subsequent ACL injury to either knee was 30% (48 of 158 players) and was especially high among players aged <21 years (23 of 46 players, 50%). After subsequent ACL injury, 34 of 48 players (71%) returned to play. In primary ACL reconstruction, the use of Ligament Augmentation and Reconstruction System grafts resulted in a faster return to play ( P = .001) but had a higher risk of subsequent revision reconstruction (risk ratio = 2.8, P = .048). Family history of ACL injury was associated with an increased risk of subsequent contralateral ACL injury (risk ratio = 3.8, P = .002). CONCLUSION::Most AFL players who underwent ACL reconstruction returned to play at least 1 AFL match. The high rate of subsequent ACL injury among AFL players demonstrates the highly demanding nature of Australian football, particularly at the elite level. The risk factors for subsequent ACL injury should be considered carefully when treatment and rehabilitation decisions are made for these high-demand athletes.