Background: Femoral-sided graft fixation in medial patellofemoral ligament (MPFL) reconstruction is commonly performed using an interference screw (IS). However, the IS method is associated with several clinical disadvantages that may be ameliorated by the use of suture anchors (SAs) for femoral fixation. Purpose: To compare the load to failure and stiffness of SAs versus an IS for the femoral fixation of a semitendinosus autograft in MPFL reconstruction. Study Design: Controlled laboratory study. Methods: Based on a priori power analysis, a total of 6 matched pairs of cadaveric knees were included. Specimens in each pair were randomly assigned to receive either SA or IS fixation. After an appropriate reconstruction procedure, the looped end of the MPFL graft was pulled laterally at a rate of 6 mm/s until construct failure. The best-fit slope of the load-displacement curve was then used to calculate the stiffness (N/mm) in a post hoc fashion. A paired t test was used to compare the mean load to failure and the mean stiffness between groups. Results: No significant difference in load to failure was observed between the IS and the SA fixation groups (294.0 ± 61.1 vs 250.0 ± 55.9; P = .352), although the mean stiffness was significantly higher in IS specimens (34.5 ± 9.6 vs 14.7 ± 1.2; P = .004). All IS reconstructions failed by graft pullout from the femoral tunnel, whereas 5 of the 6 SA reconstructions failed by anchor pullout. Conclusion: In this biomechanical study using a cadaveric model of MPFL reconstruction, SA femoral fixation was not significantly different from IS fixation in terms of load to failure. The mean load-to-failure values for both reconstruction techniques were greater than the literature-reported values for the native MPFL. Clinical Relevance: These results suggest that SAs are a biomechanically viable alternative for femoral-sided graft fixation in MPFL reconstruction.