Patients with advanced Parkinson's disease (PD) and motor complications can obtain significant symptom improvement by deep brain stimulation (DBS) of the subthalamic nucleus (STN). Very little is published, however, about longterm effect and disease evolution during DBS. We performed a 4-year prospective study of the first 22 consecutive patients treated with STN DBS. The patients were evaluated with Unified Parkinson's Disease Rating Scale Part II to VI and a patient diary concerning on-off periods and dyskinesia. Patients were scored before surgery on medication and off medication for 10 to 12 hours and in four conditions 1 and 4 years after surgery: off medication Ϯ stimulation and on medication Ϯ stimulation. In advanced PD, a significant reduction of dyskinesia and off periods was present 4 years (90%/67%) after the operation. Total motor function on stimulation alone improved 55% at 4 years, compared with baseline and activities of daily living (42%). On stimulation, significant worsening of axial symptoms and speech was present from 1 to 4 years. To evaluate disease evolution, motor symptoms were assessed off stimulation and medication for 12 hours and were found not to worsen compared with baseline, which is remarkable in an otherwise progressive disorder. Five patients developed dementia. Severe adverse events were not observed.