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Importance: Identifying the extent and predictors of burnout among occupational therapy practitioners is important so strategies can be developed to reduce burnout and mitigate associated consequences within the profession., Objective: To investigate the prevalence and determinants of burnout reported by U.S. occupational therapy practitioners., Design: Cross-sectional survey., Participants: Occupational therapy practitioners working in a wide range of clinical settings who spent at least 50% of their time in direct patient care and who had been employed continuously for more than 6 mo., Outcomes and Measures: The outcome of interest was burnout, which was measured using the Emotional Exhaustion, Depersonalization, and Personal Accomplishment subscales of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). Predictor variables included sociodemographic and workplace characteristics. The relationship between MBI-HSS subscale scores and predictor variables was jointly estimated using a multivariate multivariable linear regression analysis., Results: One hundred seventy-eight occupational therapy practitioners completed the survey. Higher perceived level of supervisor support, satisfaction with income, and educational attainment were associated with lower MBI-HSS subscale scores (ps = .001, .002, and .005, respectively)., Conclusions and Relevance: Burnout among occupational therapy practitioners can be conceptualized as an issue of workplace health and safety. Various stakeholder groups can consider potential systematic interventions involving measures to promote positive supervisor support in the workplace and salary negotiation skills for early-stage clinicians. Future research should explore broad interventions to reduce burnout among clinicians. What This Article Adds: We estimated the extent and predictors of burnout among U.S. occupational therapy practitioners. Future research, advocacy, and policy should address structural-level interventions to promote workplace cultures and conditions that can protect the occupational therapy workforce from burnout., (Copyright © 2022 by the American Occupational Therapy Association, Inc.)