We investigated how health related quality of life (HRQL) changes over time in a population-based cohort of patients with Parkinson's disease (PD), and which factors predict a lower level of HRQL in these patients. Of 227 patients with PD assessed at baseline and followed prospectively, information on HRQL-status was obtained in 111 subjects 4 years and 82 patients 8 years after inclusion. HRQL was measured by the Nottingham Health Profile (NHP). Analyses were conducted using generalized estimating equation models. The NHP total score (P < 0.001) and scores in all NHP dimensions except for sleep worsened significantly during follow-up. Steepest slope was found for the domain physical mobility (3.16, 95% CI 2.39-3.92), followed by the domains social isolation (2.22, 95% CI 1.52-2.93) and emotional reactions (1.36, 95% CI 0.74-1.97). In addition to follow-up time, higher Hoehn and Yahr staging, higher Montgomery and Aasberg Depression Rating Scale scores, and presence of insomnia at baseline were associated with lower levels of overall HRQL during follow-up. We conclude that PD has an increasing impact on HRQL as the disease progresses. During long-term follow-up, deterioration in physical mobility was the most important single factor contributing to decline in HRQL in our cohort, although distress of nonmotor character as a whole outweighed the impact of distress in physical mobility on overall HRQL. More advanced disease, higher severity of depressive symptoms, and presence of insomnia were found to be important and independent predictors of poor HRQL. (c) 2008 Movement Disorder Society.