We know it is important to avoid excessive strain on reconstructed ligaments, but we do not know how individual muscles affect cruciate ligament strain. To answer this, we studied the effect of muscle forces and external loads on cruciate ligament strain. Nine cadaveric knee joints were tested in an apparatus that allowed unconstrained knee joint motion. Quadriceps, hamstring, and gastrocnemius muscle forces were simulated. Additionally, external loads were applied such as varus-internal or valgus-external rotation forces. Cruciate ligament strain was recorded at different knee flexion angles. Activation of the gastrocnemius muscle significantly (P < 0.05) strained the posterior cruciate ligament at flexion angles larger than 40 degrees. Quadriceps muscle activation significantly strained the anterior cruciate ligament when the knee was flexed 20 degrees to 60 degrees (P < 0.01) and reduced the strain on the posterior cruciate ligament in the same flexion range (P < 0.05). Activation of the hamstring muscles strained the posterior cruciate ligament when the knee was flexed 70 degrees to 110 degrees (P < 0.05). Combined varus and internal rotation forces significantly increased anterior cruciate ligament strain throughout the flexion range (P < 0.05). The results suggest that to minimize strain on the ligament after posterior cruciate ligament surgery, strong gastrocnemius muscle contractions should be avoided beyond 30 degrees of knee flexion. The study also calls into question the use of vigorous quadriceps exercises in the range of 20 degrees to 60 degrees of knee flexion after anterior cruciate ligament reconstruction.