The purpose of this study was to analyze the effect of stereotactic neurophysiologically guided pallidotomy on health-related quality of life (QoL) of patients with Parkinson's disease (PD). Eleven patients with PD (seven men, four women; mean age, 57.2 years; mean duration of disease, 14 years) with motor complications refractory to medical therapy underwent unilateral pallidotomy. Clinical assessment was carried out a week before surgery and 4 months after the surgical procedure and was based on the Core Assessment Program for Intracerebral Transplantations protocol. QoL was measured by means of the PDQ-39. A set of rating scales (Hoehn & Yahr, Unified Parkinson's Disease Rating Scale, Schwab and England, Northwestern University Disability Scale of Walking, Abnormal Involuntary Movement Scale), timed tests, and self-evaluations of motor function and mood were applied. Improvement was found in dyskinesias (74%) and off-period disability (42%). Cardinal motor signs improved significantly (30%-59%). Four dimensions of the PDQ-39 (Mobility, ADL, Emotions, Bodily Pain) showed a significant improvement (p <0.01-0.001). The global effect on QoL, measured through the PDQ-39 Summary Index (35.3%; 95% confidence interval: 15.60-54.97), was also significant (p<0.01) but unrelated to major clinical changes. Pallidotomy significantly improves QoL in patients with advanced PD. QoL measurement provides relevant information that is probably not attainable by clinical assessment.