BACKGROUND: There is no consensus regarding the optimal rehabilitation regimen for increasing quadriceps strength after anterior cruciate ligament (ACL) injury. HYPOTHESIS: A comprehensive rehabilitation program supplemented with quadriceps strengthening in open kinetic chain (OKC) exercise will increase quadriceps strength and improve knee function without increasing static or dynamic sagittal tibial translation, compared with the same comprehensive rehabilitation program supplemented with quadriceps strengthening in closed kinetic chain (CKC) exercise, in patients with acute ACL deficiency. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Forty-two patients were tested a mean of 43 days (range, 20-96 days) after an ACL injury. Patients were randomized to rehabilitation with CKC quadriceps strengthening (11 men and 9 women) or OKC quadriceps strengthening (13 men and 9 women). Aside from these quadriceps exercises, the 2 rehabilitation programs were identical. Patients were assessed after 4 months of rehabilitation. Sagittal static translation and dynamic tibial translation were evaluated with a CA-4000 electrogoniometer. Muscle strength, jump performance, and muscle activation were also assessed. Functional outcome was evaluated by determining the Lysholm score and the Knee Injury and Osteoarthritis Outcome Score. RESULTS: There were no group differences in static or dynamic translation after rehabilitation. The OKC group had significantly greater isokinetic quadriceps strength after rehabilitation (P = .009). The hamstring strength, performance on the 1-repetition-maximum squat test, muscle activation, jump performance, and functional outcome did not differ between groups. CONCLUSIONS: Rehabilitation with OKC quadriceps exercise led to significantly greater quadriceps strength compared with rehabilitation with CKC quadriceps exercise. Hamstring strength, static and dynamic translation, and functional outcome were similar between groups. Patients with ACL deficiency may need OKC quadriceps strengthening to regain good muscle torque.