Objective: To describe the relationship between self-reported farm profitability and farmer well-being, and to explore potential implications for farmer assistance policy. Design: Cross-sectional analysis of farmers from Regional Wellbeing Survey data (wave 1, 2013) and comparison between groups. Participants: Participants were 1172 dryland farmers (35% women) and 707 irrigators (24% women). Main outcome measure: The Personal Wellbeing Index and the Kessler 10-item measure of general psychological distress. Results: There is a consistent and significant relationship between higher profitability, greater well-being and less distress among dryland farmers and irrigators. Conclusions: The relationship between farm profitability and the well-being of Australian dryland farmers and irrigators has the potential to inform farmer assistance policy. Assistance programs can be more effective if they explicitly incorporate a profitability assessment into their targeting and eligibility requirements and a well-being component into program design and delivery. Setting: Rural Australia. Intervention: Not applicable.