Manual wheelchair users rely on their upper limbs to provide independent mobility, which leads to high muscular demand on their upper extremities. This increased demand often results in shoulder pain and injury. However, the specific causes of shoulder pain are unknown. Previous work has shown that decreased shoulder muscle strength is predictive of shoulder pain onset, and others have analyzed joint kinetics, joint kinematics, propulsion technique (e.g. cadence, contact percentage) and intra-individual variability for their relation to shoulder pain or injury. However, one challenge to such studies is that the demand placed on the upper extremity cannot be measured directly, and therefore the causal mechanisms leading to pain and injury are unknown. The purpose of this study was to build upon this previous work and determine in a longitudinal setting whether there are specific kinetic, kinematic, spatiotemporal and intra-individual variability measures that predict whether a manual wheelchair user is likely to develop shoulder pain. All participants were asymptomatic for shoulder pain at the time of initial data collection and were categorized into pain and no pain groups based on who developed shoulder pain at either the 18-month or the 36-month follow-up assessment. Shoulder strength measures, handrim and joint kinetics, kinematics, spatiotemporal measures, individual standard deviations (SDs) and coefficients of variation (CVs) of the aforementioned parameters were evaluated as predictors of shoulder pain using a logistic regression model. The most important predictors of shoulder pain included shoulder adductor strength, positive shoulder joint work during the recovery phase and maximum trunk angle. Individuals who developed shoulder pain had weaker shoulder adductors, higher positive shoulder joint work during recovery, and less trunk flexion than those who did not develop pain. In addition, relative intra-individual variability (CV) was a better predictor of shoulder pain than absolute variability (SD), however future work is needed to determine when increased versus decreased intra-individual variability is more favorable for preventing shoulder pain. Thus, these predictors may provide insight into how to improve rehabilitation training and outcomes for manual wheelchair users and ultimately decrease their likelihood of developing shoulder pain and injuries.