Introduction: Simulations based on computational musculoskeletal models are powerful tools for evaluating effects of potential biomechanical interventions, such as implementing a novel prosthesis. However, the utility of simulations to evaluate effects of prosthesis design parameters on gait mechanics has not been fully realized due to lack of a readily-available limb loss-specific gait model and methods for efficiently modeling the energy storage and return dynamics of passive foot prostheses. The purpose of this study was to develop and validate a forward simulation-capable gait model with lower limb loss and a semi-active variable-stiffness foot (VSF) prosthesis. Methods: A seven-segment 28-DoF gait model was developed and forward kinematics simulations, in which experimentally-observed joint kinematics were applied and resulting foot contact forces evolved accordingly, were computed for four subjects with unilateral below-knee amputation walking with a VSF. Results: Model-predicted resultant ground reaction force (GRFR) matched well under trial-specific optimized parameter conditions (mean R2: 0.97, RMSE: 7.7% body weight (BW)) and unoptimized (subject-specific, not trial-specific) parameter conditions (mean R2: 0.93, RMSE: 12% BW). Simulated anterior-posterior center of pressure demonstrated mean R2 = 0.64 and RMSE = 14% foot length. Simulated kinematics remained consistent with input data (0.23 deg RMSE, R2 > 0.99) for all conditions. Conclusions: These methods may be useful for simulating gait of individuals with lower limb loss and predicting GRFR with novel VSF prostheses. Such data are useful to optimize user-specific prosthesis design parameters.