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The prevalence of burnout and depression in anesthesiology residents has not been determined. It is also unknown whether anesthesiology resident burnout/depression may affect patient care and safety. The primary objective of this study was to determine the prevalence of burnout and depression in anesthesiology residents in the United States. We hypothesized that residents at high risk of burnout and/or depression would report more medical errors as well as a lower rate of following principles identified as the best practice of anesthesiology.A cross-sectional survey was sent to 2773 anesthesiology residents in the United States. The questionnaire was divided into 5 parts examining trainees’ demographic factors, burnout (Maslach Burnout Inventory), depression (Harvard depression scale), 10 questions designed to evaluate best practice of anesthesiology, and 7 questions evaluating self-reported errors. Best practices and self-reported error rates were compared among subjects with a high risk of burnout only, high risk of depression only, high risk of burnout and depression, and low risk of burnout and depression. Pairwise comparisons were considered significant at P < 0.004 and confidence intervals (CIs) reported at 99.6%.There were 1508 (54%) resident responds. High burnout risk was found in 41% (575 of 1417) of respondents. Working >70 hours per week, having >5 drinks per week, and female gender were associated with increased burnout risk. Twenty-two percent (298 of 1384) screened positive for depression. Working >70 hours of work per week, smoking, female gender, and having >5 drinks per week were associated with increased depression risk. Two hundred forty (17%) respondents scored at high risk of burnout and depression, 321 (23%) at high risk of burnout, 58 (4%) at high risk of depression only, and 764 (56%) at low risk of burnout or depression. Median best practice scores (maximum = 30) for residents at high risk of burnout (difference −2; 99.6% CI, −1 to −2; P < 0.001) or high risk of burnout and depression (difference −4; 99.6% CI, −3 to −6; P < 0.001) were lower than scores of residents at low risk for burnout or depression. Thirty-three percent of respondents with high burnout and depression risk reported multiple medication errors in the last year compared with 0.7% of the lower-risk responders (P < 0.001).Burnout, depression, and suicidal ideation are very prevalent in anesthesiology residents. In addition to effects on the health of anesthesiology trainees, burnout and depression may also affect patient care and safety.