The COVID-19 pandemic has affected clinician health and retention. To describe trends in burnout from 2019 through 2021 with associated mitigating and aggravating factors. Cross-sectional surveys were sent to physicians and advanced practice clinicians throughout 120 large US health care organizations between February 2019 and December 2021. From 56 090 surveys, there were 20 627 respondents. Work conditions and COVID-19. Surveys measured time pressure, chaos, work control, teamwork, electronic health record use, values alignment, satisfaction, burnout, intent to leave, and in 2021, feeling valued. Multivariate regressions controlling for gender, race and ethnicity, years in practice, and role determined burnout, satisfaction, and intent-to-leave correlates. Of the 20 627 respondents (median response rate, 58% [IQR, 34%-86%; difference, 52%]), 67% were physicians, 51% female, and 66% White. Burnout was 45% in 2019, 40% to 45% in early 2020, 50% in late 2020, and 60% in late 2021. Intent to leave increased from 24% in 2019 to more than 40% as job satisfaction decreased. Higher burnout was seen in chaotic workplaces (odds ratio [OR], 1.51; 95% CI, 1.38-1.66; P < .001) and with low work control (OR, 2.10; 95% CI, 1.91-2.30; P < .001). Higher burnout was associated with poor teamwork (OR, 2.08; 95% CI, 1.78-2.43; P < .001), while feeling valued was associated with lower burnout (OR, 0.22; 95% CI, 0.18-0.27; P < .001). In time trends, burnout was consistently higher with chaos and poor work control. For example, in the fourth quarter of 2021 burnout was 36% (95% CI, 31%-42%) in calm environments vs 78% (95% CI, 73%-84%) if chaotic (absolute difference, 42%; 95% CI, 34%-49%; P < .001), and 39% (95% CI, 33%-44%) with good work control vs 75% (95% CI, 69%-81%) if poor (absolute difference, 36%; 95% CI, 27%-44%; P < .001). Good teamwork was associated with lower burnout rates (49%; 95% CI, 44%-54%) vs poor teamwork (88%; 95% CI, 80%-97%; absolute difference, 39%; 95% CI, 29%-48%; P < .001), as was feeling valued (37%; 95% CI, 31%-44%) vs not feeling valued (69%; 95% CI, 63%-74%; absolute difference, 32%; 95% CI, 22%-39%; P < .001). Results of this survey study show that in 2020 through 2021, burnout and intent to leave gradually increased, rose sharply in late 2021, and varied by chaos, work control, teamwork, and feeling valued. Monitoring these variables could provide mechanisms for worker protection.