Objectives: To develop a prediction algorithm for soft tissue changes after orthognathic surgery that would result in accurate predictions (1) regardless of types or complexity of operations and (2) with a minimum number of input variables. Materials and Methods: The subjects consisted of 318 patients who had undergone the surgical correction of Class II or Class III malocclusions. Two multivariate methods—the partial least squares (PLS) and the sparse partial least squares (SPLS) methods—were used to construct prediction equations. While the PLS prediction model included 232 input variables, the SPLS method included a reduced number of variables generated by a handicapping algorithm via the sparsity control. The accuracy between the PLS and SPLS models was compared. Results: There were no significant differences in prediction accuracy depending on surgical movements, the sex of the subjects, or additional surgeries. The predictive performance with a reduced set of 34 input variables chosen using the SPLS method was statistically indistinguishable from the full set of variables with the original PLS prediction model. Conclusions: The prediction method proposed in the present study was accurate for a wide range of orthognathic surgeries. A reduced set of input variables could be selected through the SPLS method while simultaneously maintaining a prediction level that was as accurate as that of the original PLS prediction model.