BACKGROUND Removable partial dentures (RPDs) provide a cost-effective treatment for millions of partially edentulous patients worldwide. However, they often fail because of loss of retention. One reason for this problem is lack of precise guidelines for designing retentive RPDs. OBJECTIVE The purpose of this in vitro study was to determine the forces produced by food and clasps during mastication to develop an algorithm for predicting RPD retention and to help determine the optimal number of clasps. METHODS The forces that food exerts on acrylic resin teeth during simulated mastication and the retention forces provided by clasps (wrought wire, circumferential, and I-bar) engaging on teeth were measured using a universal testing machine. A statistical analysis was performed with a 1-way ANOVA and repeated-measures ANOVA while the developed algorithm was evaluated by using sensitivity and specificity analysis. RESULTS The force exerted by food mastication on each individual tooth ranged between 1.7 and 12.2 N, depending on the type of tooth, tooth anatomy, occlusion, and food. The retention force of the clasps after cyclic testing ranged between 2.9 and 14.5 N, depending on the type of tooth abutment and clasp. Using these measurements, an algorithm was developed to predict RPD retention. The algorithm was confirmed experimentally on 36 RPDs, showing a sensitivity of 96%, specificity of 100%, and an accuracy of 97%. CONCLUSIONS The forces generated by food mastication on teeth varied according to the type of tooth, occlusion, and food. The retention force of RPD clasps varied according to the type of tooth and clasp. An algorithm for predicting RPD retention and determining the optimal number of clasps was developed and validated experimentally.