The objective of this study was to evaluate the initial fixation strength of a biodegradable interference screw compared with press-fit fixation and a titanium interference screw in anterior cruciate ligament reconstruction using a bone-patellar tendon-bone graft. Porcine lower limbs were used. The specimens underwent 500 loading cycles between 60 and 250 N. This corresponds to loads in the graft during aggressive rehabilitation. Thereafter, intact specimens were loaded to failure. Failure mode was defined by visual analysis. Under cyclic loads none of the interference screw fixations failed. In the press-fit group (angle between load axis and tunnel axis 80°), five specimens failed. The mean maximal load to failure was 945 N (±87) for the titanium screw, 797 N (±60) for the biodegradable screw, and 708 N (±211) for the five press-fit specimens that did not fail during cyclic loading. With respect to primary fixation strength, biodegradable screws are a reasonable alternative to titanium interference screws. The press-fit fixation did not provide a secure fixation in all cases. Five press-fit specimens failed under cyclic loads comparable with those seen under conditions of accelerated rehabilitation.