Image-guided neuronavigation has largely replaced stereotactic frames when precise, real-time anatomic localization is required during neurosurgical procedures. However, some procedures, including placement of deep-brain stimulation (DBS) leads for the treatment of movement disorders, are still performed using frame-based stereotaxy. Despite the demonstration of comparable accuracy between frame-based and "frameless" image-guided approaches, the clinical efficacy of frameless DBS placement has never been reported. To analyze the outcomes of subthalamic nucleus (STN) DBS using the frameless technique for the treatment of Parkinson's disease (PD). Of 31 subjects (20 men) with PD for 10 ± 4 years, 28 had bilateral STN DBS and 3 had unilateral STN DBS. The Unified Parkinson's Disease Rating Scale (UPDRS) motor scale (III) and total medication doses were assessed before surgery on and off medication and off medication/ON DBS (off/ON) after 6 to 12 months of STN DBS. There was a 58% improvement from bilateral STN DBS in the UPDRS III (40 ± 16 preoperatively off, 17 ± 11 off/ON) 9.6 ± 1.9 months after surgery (P < .001). This compared favorably with the published outcomes using the frame-based technique. All motor subscores improved significantly (P < .01). The mean reduction in medication was 50%. No intraoperative complications occurred, but one subject with hypertension died of a delayed hemorrhage postoperatively. Two subjects developed postoperative infections that required lead removal and antibiotics. Bilateral STN DBS for PD performed by an experienced team using a frameless approach results in outcomes comparable to those reported with the use of the frame-based technique.