Factors associated with upper limb prosthesis adoption are not well understood. In this study, we explored how prosthesis usability experience relates to the extent of prosthesis adoption through the development of a structural equation model (SEM). First, items related to prosthesis usability were developed and refined using cognitive testing and pilot testing and employed in a survey of 402 prosthesis users (mean age 61.7 (sd 14.4), 77.1% Veterans). The SEM examined two unidimensional latent constructs: Prosthesis Usability Experience and Prosthesis Adoption–and each had multiple measured indicators. SEMs tested direct as well as moderating and mediating effects between the latent constructs and covariates related to demographics and prosthesis type. SEM found a significant positive association between Prosthesis Usability Experience and Extent of Prosthesis Adoption. Several covariates had direct effects on prosthesis adoption: 1) Extent of Prosthesis Adoption was lower for those with transhumeral and shoulder amputation, and higher for those with bilateral amputation, compared to the reference group with unilateral transradial amputation and 2) Myoelectric multiple degree of freedom (multi-DOF) prosthesis use was associated with lower Extent of Prosthesis Adoption, compared to body-powered prosthesis use. Myoelectric multi-DOF use also modified the effect of Prosthesis Usability Experience on Extent of Prosthesis Adoption. For those with bilateral ULA, the strength of the relationship between Prosthesis Usability Experience and Extent of Prosthesis Adoption was reduced. Findings suggest that in order to increase prosthesis adoption, prosthetics developers and rehabilitation providers should focus on implementing strategies to improve prosthesis usability experience. New Prosthesis Usability Experience measures could be used to identify persons at greater risk for poor prosthesis adoption and target interventions to increase prosthesis use.