Parkinson's disease (PD) can be symptomatically controlled with standard treatments; however, after a few years, this response typically declines and most patients develop motor complications. We carried out a prospective practice-based study to evaluate the evolution appearance and evolution of motor complications in 64 de novo PD patients over 5 years and in 38 PD patients over 10 years. We studied untreated patients from initial assessment at basal conditions and evaluated every 6 months thereafter with treatment (levodopa versus other drugs). The follow-up assessments were performed with the Unified Parkinson's Disease Rating Scale (UPDRS). At each assessment, patients were monitored regarding the development of dyskinesias, motor fluctuations, freezing, loss of postural reflexes, and cognitive impairment. We observed a significant improvement in UPDRS scores during the first year, then a progressive decline, more evident after the third year. Motor complications increased after the third year, and at the end of the survey (tenth year); drug-induced dyskinesias and motor fluctuations were experienced (71.1 and 94.7%, respectively). After the first decade, many complications arose from the non-levodopa–responsive features of the disease (cognitive impairment was present in 52.6% and gait freezing in 71.1%). Initial medication may influence medium-term complications but not long-term problems. Most long-term disabling problems of PD were related to non-levodopa-responsive features. © 2010 Movement Disorder Society.