Gait modifications, such as lateral trunk lean (LTL), medial knee thrust (MKT), and toe-in gait (TIG), are frequently investigated interventions used to slow the progression of knee osteoarthritis. The Lerner knee model was developed to estimate the tibiofemoral joint reaction forces (JRF) in the medial and lateral compartments during gait. These models may be useful for estimating the effects on the JRF in the knee as a result of gait modifications. We hypothesized that all gait modifications would decrease the JRF compared to normal gait. Twenty healthy individuals volunteered for this study (26.7 ± 4.7 years, 1.75 ± 0.1 m, 73.4 ± 12.4 kg). Ten trials were collected for normal gait as well as for the three gait modifications: LTL, MKT, and TIG. The data were used to estimate the JRF in the first and second peaks for the medial and lateral compartments of the knee via opensim using the Lerner knee model. No significant difference from baseline was found for the first peak in the medial compartment. There was a decrease in JRF in the medial compartment during the loading phase of gait for TIG (6.6%) and LTL (4.9%) and an increasing JRF for MKT (2.6%). but none was statistically significant. A significant increase from baseline was found for TIG (5.8%) in the medial second peak. We found a large variation in individual responses to gait interventions, which may help explain the lack of statistically significant results. Possible factors influencing these wide ranges of responses to gait modifications include static alignment and the impacts of variation in muscle coordination strategies used, by participants, to implement gait modifications.