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BACKGROUND: Burnout is a major challenge in health care, but its prevalence has not been evaluated in practicing respiratory therapists (RTs). The purpose of this study was to identify RT burnout prevalence and factors associated with RT burnout. METHODS: An online survey was administered at 26 centers in the United States between January and March 2021. Validated quantitative cross-sectional surveys were used to measure burnout and leadership domains. The survey was sent to department directors and distributed by the department directors to their staffs. Data analysis was descriptive, and logistic regression analysis was performed to evaluate risk factors, expressed as odds ratios (OR), for burnout. RESULTS: The survey was distributed to 3,010 RTs; the response rate was 37%. Seventy-nine percent of the respondents reported burnout, 10% with severe, 32% with moderate, and 37% with mild burnout. Univariate analysis revealed that those with burnout worked more hours per week, worked more hours per week in the ICU, primarily cared for adult patients, primarily delivered care via RT protocols, reported inadequate RT staffing, reported being unable to complete assigned work, had more frequent exposure to COVID-19 (coronavirus disease 2019), had a lower leadership score, and fewer had a positive view of leadership. Logistic regression revealed that burnout climate (OR 9.38; P < .001), inadequate RT staffing (OR 2.08 to 3.19; P = .004 to .05), unable to complete all work (OR 2.14 to 5.57; P = .003 to .02), and missed work for any reason were associated with an increased risk of burnout (OR 1.96; P = .007). Not providing patient care (OR 0.18; P = .02) and a positive leadership score (.55; P = .02) were associated with a decreased risk of burnout. CONCLUSIONS: Burnout was common among the RTs in the midst of the COVID-19 pandemic. Good leadership was protective against burnout, whereas inadequate staffing, an inability to complete work, and a burnout climate were associated with burnout.