OBJECTIVE: This study aimed to compare stress, burnout, stressors, and protective factors among regional- and metropolitan-based Australian medical doctors. METHOD: A mixed methods design was utilized with 252 Australian medical doctors completing an online questionnaire package. A subsample also completed qualitative interviews. RESULTS: Stress was significantly higher among doctors compared with population norms. Over half of doctors reported burnout on one or more dimensions. The strongest unique predictors were being female, working late, and work-family conflict. Qualitatively, 12 stressors (e.g., training and competition, workload, and time management) and 9 protective subthemes (e.g., being well resourced, clinical interest) emerged across system-level, clinical environment-level, and individual factor and personal response themes. CONCLUSIONS: Stress and burnout among doctors are alarmingly high and both system/organization-level (e.g., communication systems, workload, flexible work arrangements) and individual-level (e.g., fostering resilience/coping strategies) predictors are implicated by our results. These may be useful targets for future interventions.