Determinants of health-related quality of life (HRQoL) were assessed in 115 Brazilian patients (56.5% males; mean age 62.5 years) with Parkinson's disease (PD). Hoehn and Yahr (H&Y) staging, Scales for Outcomes in Parkinson's Disease-Motor Scale (SCOPA-MS), Cumulative Illness Rating Scale-Geriatrics, Hospital Anxiety and Depression Scale (HADS), Parkinson's Disease Questionnaire (PDQ-39), and SCOPA-Psychosocial Questionnaire (SCOPA-PS) were applied. Median H&Y was 3 and the SCOPA-MS score was 25.6+/-13.1. The proportion of patients who scored > or =11 points in the HADS-Depression and HADS-Anxiety subscales were 47% and 30.4%, respectively. In the multivariate model, HADS-Anxiety or HADS-Depression (p<0.0001), disability (SCOPA-MS II) (p=0.0001) and comorbidity (p=0.0005) were independently associated to PDQ-39 and SCOPA-PS. Mood disturbances were the main determinants of HRQoL.