PURPOSE: To examine the rate of (1) second anterior cruciate ligament (ACL) rupture (graft rupture or contralateral ACL rupture) and (2) graft rupture alone in patients with generalized joint hypermobility (GJH) at 12 months, at 24 months, and at the longest available time (LAT) following return to sport (RTS) after ACL reconstruction depending on graft choice, that is, hamstring tendon (HT) autograft or bone-patellar tendon-bone (BPTB) autograft. METHODS: Data were extracted from a rehabilitation registry that comprised patients who had undergone ACL reconstruction between 2014 and 2022. Patients with GJH aged between 16 and 50 years who had minimum 24-month follow-up following RTS after ACL reconstruction with HT autograft (GJH-HT) or BPTB autograft (GJH-BPTB) were included. A Cox proportional hazard regression model was used to examine the rate of (1) second ACL rupture (graft rupture or contralateral ACL rupture) and (2) graft rupture alone at 12 months, at 24 months, and at the LAT after RTS. RESULTS: This study included 82 patients (54 in the GJH-HT group and 28 in the GJH-BPTB group), of whom 72.0% were female patients, and the average age was 22.7 ± 7.4 years. The proportion of second ACL ruptures was greater in the GJH-HT group than in the GJH-BPTB group at 12 months (11 of 54 [20.4%] vs 0 of 28 [0%], P = .013), at 24 months (13 of 54 [24.1%] vs 1 of 28 [3.6%], P = .028), and at the LAT (16 of 54 [29.6%] vs 2 of 28 [7.1%], P = .024) after RTS. The rate of second ACL rupture was greater in the GJH-HT group than in the GJH-BPTB (hazard ratio = 4.98, P = .032) at the LAT after RTS. The proportion of patients with graft rupture was greater in the GJH-HT group than in the GJH-BPTB group at 12 months (8 of 54 [14.8%] vs 0 of 28 [0%], P = .046), at 24 months (10 of 54 [18.5%] vs 0 of 28 [0%], P = .013), and at the LAT (12 of 54 [22.2%] vs 0 of 28 [0%], P = .006) after RTS. CONCLUSIONS: An over 4 times greater rate of second ACL rupture after RTS was reported for patients with GJH who underwent ACL reconstruction with HT autograft compared with BPTB autograft. Patients with GJH who were treated with BPTB autograft for ACL reconstruction did not experience graft rupture after RTS. LEVEL OF EVIDENCE: Level III, retrospective study.