In musculoskeletal modelling, adjusting model parameters is challenging. This paper proposes a multivariate statistical methodology to adjust muscle force-generating parameters optimally. Dynamic residuals are minimized as muscle force-generating parameters are varied (maximal isometric force, optimal fiber length, tendon slack length and pennation angle). First, a sensitivity and a Pareto analyses are carried out in order to sort out and screen the set of parameters having the greatest influence regarding the dynamic residuals. These parameters are then used to create a response surface following a Design of Experiments (DoE) approach. Finally, this surface is used to determine the optimum levels of the design variables (muscle forcegenerating parameters). The proposed methodology is illustrated by the adjustment of a three-dimensional musculoskeletal model of a sheep forelimb. After adjustment, the reserve actuator values of the elbow and wrist joints were reduced, on average, by 18%, and 16%, respectively. These results demonstrate that the use of multivariate statistical strategies is an effective way to adjust model parameters optimally while reducing dynamic inconsistencies. This study constitutes a step towards a more robust methodology in musculoskeletal modelling, focusing on muscular parameter tuning.