BACKGROUND:Lifestyles are involved in the pathogenesis of depression and many of these factors can be modified for the potential prevention of depression. Our aim was to assess the association between a healthy-lifestyle score, that includes some less-studied lifestyle indicators, and the risk of depression. METHODS:We followed 14,908 participants initially free of any history of depression in the "Seguimiento Universidad de Navarra" (SUN) cohort. Information was collected biennially from 1999 to December 2016. We calculated a healthy-lifestyle score (0-10 points), previously associated with cardioprotection, by giving one point to each of the following components: never smoking, physical activity (> 20 METs-h/week), Mediterranean diet adherence (≥ 4 points), healthy body mass index (≤ 22 kg/m2), moderate alcohol consumption (women 0.1-5 g/d; men 0.1-10 g/d of ethanol), avoidance of binge drinking (never more than 5 alcoholic drinks in a row), low television exposure (≤ 2 h/d), short afternoon nap (≤ 30 min/day), time spent with friends (>1 h/d) and working at least 40 h/week. RESULTS:During a median follow-up of 10.4 years, we observed 774 new cases of major depression among participants initially free of depression. The highest category (8-10 factors) showed a significant inverse association with a 32% relative risk reduction for depression compared to the lowest category (0-3 factors) (multivariable-adjusted hazard ratio: 0.68; 95% CI:0.49-0.95) (p for trend = 0.010). CONCLUSIONS:Adopting a healthy-lifestyle was associated with a lower risk of incident depression in the SUN cohort. This index, including ten simple healthy lifestyle habits, may be useful for a more integrative approach to depression prevention.