Purpose: The purpose of this study was to evaluate the effect of bioabsorbable interference screw diameter on the pullout strength and failure mode for femoral tunnel fixation in primary anterior cruciate ligament reconstruction (ACLR) at time zero fixation using bone-patellar tendon-bone (BTB) autograft in a cadaveric model. Methods: Twenty-four fresh-frozen cadaveric knees were obtained from 17 different donors. Specimens were allocated to three different treatment groups (n = 8 per group) based on interference screw diameter: 6 mm, 7 mm, or 8 mm biocomposite interference screw. All specimens underwent dual energy X-ray absorptiometry (DEXA) scanning prior to allocation to ensure no difference in bone mineral density among groups (n.s.). All specimens underwent femoral-sided ACLR with BTB autograft. Specimens subsequently underwent mechanical testing under monotonic loading conditions to failure. The load to failure and failure mechanism were recorded. Results: The mean pullout force (N) at time zero for each group was 309 ± 213 N, 518 ± 313 N, and 541 ± 267 N for 6 mm, 7 mm, and 8 mm biocomposite interference screw diameter, respectively (n.s.). One specimen in the 6 mm group, two specimens in the 7 mm group, and one specimen in the 8 mm group failed by screw pullout. The remainder in each group failed by graft failure (n.s.). Conclusion: Biocomposite interference screw diameter did not have a significant influence on fixation pullout strength or failure mode following femoral tunnel fixation using BTB autograft at time zero. A 6 mm interference screw can improve preservation of native bone stock, increase potential for biologic healing, and decrease the risk of damage to the graft during insertion without significantly compromising fixation strength. This study supports the use of smaller 6 mm interference screw diameter options for femoral tunnel fixation in ACLR.