Interference screw fixation is one of the most common methods for ligament reconstruction. Although the advantages and clinical outcomes of this procedure have been widely reported, post-surgical complications often arise. The purpose of this study was to evaluate a new femoral fixation device, the Endoscrew, for anterior cruciate ligament (ACL) reconstruction. We performed a mechanical test in accordance with American Society for Testing and Materials (ASTM) standards and an in vitro biomechanical study. An axial pullout test was conducted to evaluate the mechanical properties of the new device and the interference screw when implanted in solid rigid polyurethane foam test blocks. The biomechanical test used porcine femora to evaluate the initial fixation strength between these two implants. The maximum pullout force of the interference screw group [722.05 ± 130.49 N (N)] was significantly greater (p < 0.01) than the Endoscrew group (440.79 ± 26.54 N) when implanted in polyurethane foam 320 kg/m3 density. With polyurethane foam 160 kg/m3 density, the maximum pullout forces were (242.61 ± 37.36 N) (p < 0.001) and (99.33 ± 30.01 N) for the interference screw group and Endoscrew group, respectively. In the in vitro mechanical study, the Endoscrew (646.39 ± 72.38 N) required a significantly greater ultimate load prior to failure (p < 0.05) when compared with the interference screw (489.72 ± 138.64 N). With regard to pullout stiffness, there was no statistically significant difference (p < 0.13) between the Endoscrew group (99.15 ± 12.16 N/mm) and the interference screw group (87.96 ± 11.12 N/mm). The cyclic stiffness was also not significantly different (p < 0.44) between the Endoscrew group (93.09 ± 16.07 N/mm) and the interference screw group (85.78 ± 14.76 N/mm). The axial pullout test showed that the strength of the Endoscrew was close to the fixation strength required for daily activities, but it is inappropriate for use in osteoporotic patients. The in vitro study showed that the Endoscrew has a superior initial mechanical fixation over the biodegradable interference screw.