Burnout in the health care industry is a potential hazard that has reached epidemic proportions mostly among doctors in practice and training. Burnout has enormous consequences on doctors, patients, and health care institutions. This study aimed to determine the prevalence and predictors of burnout among resident doctors in Enugu State, Nigeria. This was a mixed-method study of 420 resident doctors in tertiary hospitals in Enugu State, Nigeria. Data were collected using Oldenburg Burnout Inventory and in-depth interviews of chief resident doctors of selected departments. Data were analyzed using IBM statistical package 23.0 and Nvivo 11. Test of significance was set at 0.05. The mean age of participants was 34.11 ± 5.08 years. The prevalence of burnout groups among resident doctors was 84.3% in the burnout group, 4.8% in the disengagement group, 6.9% in the exhaustion group, and 4.0% in the non-burnout group. Gender (OR = 1.861, C.I = 1.079-3.212), duration of training (OR = 1.740, C.I = 1.008-3.005), and working hours (OR = 2.982, C.I = 1.621-5.487) were the predictors of burnout; only working hours (OR = 0.279, C.I = 0.091-0.0862) was the predictor of disengagement; and gender (OR = 0.248, C.I = 0.107-0.579) was the predictor of exhaustion. Heavy workloads, long working hours, migration, poor working environment, job insecurity, poor remuneration, and management style were identified factors of burnout. There was high prevalence of burnout among resident doctors, predicted by gender, duration of training, and working hours. Interventions are needed to reduce burnout, prevent the "brain drain", and improve resident doctors' overall well-being.