Studies reveal that most physicians report symptoms of burnout. Less is known about burnout in mid-career medical faculty specifically. To characterize burnout and its risk factors, particularly differences by gender, among mid-career medical faculty. Between August 2021 and August 2022, a survey was sent to 1430 individuals who received new National Institutes of Health K08 and K23 career development awards from 2006 to 2009. Data were analyzed between June and October 2023. Personal and work-related burnout as evaluated using the Copenhagen Burnout Inventory (CBI). The CBI score ranges from 0 to 100, with a score of 50 or higher indicating a high degree of burnout. Multivariable models were used to investigate associations between burnout and participant characteristics, including race and ethnicity, sexual orientation and gender identity, academic rank, work climate, experiences of workplace sexual harassment, sleep hours, work and domestic caregiving time, and time allocation changes in work and domestic work hours compared with before the COVID-19 pandemic. Work climate was evaluated by a general climate elements scale assessing elements such as friendliness, respect, and collegiality, and a diversity, equity, and inclusion climate elements scale assessing elements such as homogeneity, sexism, and homophobia; higher scores indicated a more favorable view of the climate. In all, 1430 surveys were sent, 926 candidates responded (65% response rate), and the analytic cohort was limited to the 841 respondents who were still in academic medicine (50.7% men). Burnout was significantly more common for women than men (mean [SD] CBI personal scores, 46.6 [19.4] vs 37.5 [17.2]; P < .001; mean [SD] CBI work-related scores, 43.7 [20.4] vs 34.6 [19.7]; P < .001). In multivariable models, personal burnout was significantly more likely for women (adjusted odds ratio [AOR], 2.29 [95% CI, 1.54-3.41]; P < .001) and with more weekly hours of patient care (AOR, 1.07 [95% CI, 1.00-1.15] for each 5-hour increase; P = .04). Personal burnout was less likely with more nightly sleep hours (AOR, 0.68 [95% CI, 0.56-0.81] for each 1-hour increase; P < .001) and with an improved general work climate rating (AOR, 0.64 [95% CI, 0.48-0.85] for each 1-point increase in general work climate scale score; P = .002). Work-related burnout was also significantly more likely for women than men (AOR, 1.77 [95% CI, 1.17-2.69]; P = .007). Greater work-related burnout was associated with an increase of 8 or more work hours per week compared with before the COVID-19 pandemic (AOR, 1.87 [95% CI, 1.13-3.08]; P = .01), more weekly hours of patient care (AOR, 1.11 [95% CI, 1.03-1.19] for each 5-hour increase; P = .007), and a workplace sexual harassment experience in the past 2 years (AOR, 1.71 [95% CI, 1.11-2.62]; P = .01). Work-related burnout was significantly less likely with more nightly sleep hours (AOR, 0.80 [95% CI, 0.66-0.96] for each 1-hour increase; P = .02) and with an improved general work climate rating (AOR, 0.49; [95% CI, 0.36-0.65] for each 1-point increase in general work climate scale score; P < .001). This survey study of K grant awardees revealed substantial rates of burnout among mid-career medical faculty, and burnout rates differed by gender. Evidence-based interventions are needed to realize the benefits of workforce diversity and vitality.