Positive motivational attitudes protect against depressive symptoms in young adults. This study examined the longitudinal relationship between motivation to achieve important life goals and depression in a sample of young adult university students, who are at higher risk of developing psychiatric disorders and adopting unhealthy behaviours than their age peers who are not attending university. The participants were 228 Italian undergraduates who completed an online self-report questionnaire twice during a one-year period. Measures included positive motivational attitudes, depressive feelings, body mass index, smoking, alcohol consumption, cannabis use, subjective family income and satisfaction with academic choice. A cross-lagged longitudinal model demonstrated that higher motivation predicted lower depression after one year. No other covariate effects were observed. The results confirm that motivation protects against mental health problems during higher education and is a better predictor of mental health than health-related risk factors. Encouraging undergraduates to invest effort in achieving important goals may prevent the onset of depressive disorders.