To compare the clinical results of anterior cruciate ligament reconstruction in female patients using quadruple-looped hamstring autograft versus patellar tendon autograft at minimum 2-year follow-up. Case series. A prospective clinical review was performed to compare the results of ACL reconstruction with hamstring versus patellar tendon autograft in a group of female patients. Exclusion criteria included chronic injuries (greater than 3 months), associated collateral ligament injuries, Workers' Compensation or litigation cases, and bilateral anterior cruciate ligament injuries. There were 39 female patients in the hamstring group (average follow-up, 40.9 months) and 37 female patients in the patellar tendon group (average follow-up, 52 months). Both types of grafts were fixed with an EndoButton proximally and with sutures tied over a post or button distally. The postoperative rehabilitation regimen was identical for both groups. Objective parameters evaluated included preinjury and postoperative Tegner and Lysholm scores, side-to-side KT-1000 maximum-manual arthrometer differences, and clinical examination including Lachman and pivot-shift tests. Graft failure was defined by any one of the following: a KT-1000 difference of greater than 5 mm, a 2+ Lachman, a 1+ or greater pivot shift, or revision surgery. The failure rate in the hamstring group was 23% versus 8% in the patellar tendon group, which was not statistically significant (P >.1). Comparison of preinjury Tegner activity scores to postoperative scores revealed that patients in the hamstring group did not return to their preinjury level of activity (preinjury 6.54 v postoperative 5.17) as well as patients in the patellar tendon group (preinjury 6.20 v postoperative 6.59). Patients in the hamstring group had a significant increase in pain compared with the patellar tendon group (P =.034). Although not statistically significant, the hamstring group had more failures, more laxity on clinical examination, and more patients with larger KT-1000 arthrometer differences. These results indicate a trend toward increased graft laxity in female patients undergoing reconstruction with hamstring autograft compared with patellar tendon when evaluated by a single surgeon using similar fixation techniques at short- to medium-range follow-up. More studies with larger patient numbers using current fixation techniques are necessary to confirm these findings.