Objective: To quantify the benefit of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on contralateral, ipsilateral, and axial symptoms of advanced Parkinson's disease. Methods: Thirty-seven patients received unilateral STN DBS and were rated on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed tests of motor function in the "practically defined off" state at baseline and at 3, 6, and 12 months postoperatively. Results: UPDRS motor scores improved significantly at 3, 6, and 12 months relative to the preoperative baseline (P < 0.001, 37.1% at 1 year). There was improvement in the contralateral UPDRS subscores (P < 0.001, 54.6% at 1 year), and although contralateral benefit was larger on all outcome measures, ipsilateral benefit was present at 3 and 6 months on the UPDRS subscore (P = 0.013 and 23.5%, P = 0.005 and 27.7%, respectively). A trend toward ipsilateral benefit was present on the UPDRS subscore at 12 months; however, the effect was not statistically significant. Two timed tests of motor function in the upper extremities showed significant ipsilateral benefit in bradykinesia at 12 months (P < 0.001 and P = 0.014, respectively). Significant benefit was also observed in the UPDRS part 2 "off" medications and the UPDRS part 4 after unilateral STN DBS at 12 months (both P < 0.001). Conclusion: Considering the bilateral effects and tolerability of unilateral STN DBS, unilateral stimulation followed by a contralateral procedure later, if necessary, is a reasonable option for patients with advanced Parkinson's disease, especially with prominent asymmetry. © 2009 by the Congress of Neurological Surgeons.