BACKGROUND AND PURPOSE: Non-motor symptoms including depression are important features of Parkinson's disease (PD). We aim to address the relationship between major life events and depression amongst PD patients free of depressive symptoms at baseline. METHODS: New-onset PD patients from California were recruited in 2001-2007 and followed up for 3-4 years. The participants (n = 221) were examined by neurologists and responded to comprehensive interviews that included major life events, social support, and coping measures from validated scales. Major depression was assessed using the Structured Clinical Interview for the DSM-IV depression module (SCID). RESULTS: More than half of all patients had experienced major life events since diagnosed with PD, and 22 patients developed a major depression. The number of life events was associated with risk of depression in an exposure-dependent manner, with each additional event being associated with a 56% higher risk of depression (95% CI: 1.23-1.98). Most individual life events were associated with a two- to eight-fold higher risk of depression. Patients with low social support or coping capacities seemed to be particularly susceptible to developing depression after experiencing major life events. CONCLUSIONS: Life events play an important role for onset of depression in patients with PD; an effect that seems to be modulated by social support and coping capacities and these factors may therefore be important to assess in order to identify patients with PD at high risk of depression and provide effective interventions.