This study investigated the impact of a combination of axial compressive and anterior-posterior tibial loads on the in situ forces in the anterior cruciate ligament. An axial compressive load is believed to contribute to increased stability of the knee joint; however, its effect on in situ forces in the anterior cruciate ligament has not been clearly defined, to our knowledge. It was hypothesized that the application of an axial compressive load, when combined with an anterior tibial load, would result in larger in situ forces in the anterior cruciate ligament than those caused by an isolated anterior tibial load. With use of a porcine knee model, the results confirmed this hypothesis; the addition of a 200 N axial compressive load to a 100 N anterior tibial load increased knee stability by reducing anterior-posterior tibial translation and internal-external tibial rotation and also caused a significant increase in in situ forces in the anterior cruciate ligament (p < 0.05). Specifically, there was a 34% increase in the in situ force at 30 degrees of flexion, a 68% increase at 60 degrees of flexion, and an 84% increase at 90 degrees of flexion compared with those for an isolated anterior tibial load of 100 N. Additionally, there was a statistically significant increase of the in situ forces in the anterior cruciate ligament at 60 and 90 degrees as compared with those at 30 degrees. These results suggest that axial compressive loads on the knee may play a role in injury of the anterior cruciate ligament when the knee is flexed.