INTRODUCTION: Although deep brain stimulation (DBS) in the ventrolateral thalamus is an effective treatment for severe intention tremor, the optimal site for stimulation is the subject of ongoing debate. METHODS: DBS electrodes were implanted into one of five tracks explored by microrecording and microstimulation in seven patients with essential tremor and six patients with multiple sclerosis. Stereo-tactic coordinates of each electrode contact were determined from stereotactic x-rays, and the efficacy of each contact was assessed. RESULTS: Contacts located ventral to the intercommissural plane reduced lateralized Fahn scores by 63.6 ± 21.1% (right) and 67.9 ± 18.3% (left), whereas dorsal contacts were less effective (20.5 ± 16.4% and 17.6 ± 16.2%, respectively). Similarly, only stimulation below the intercommissural plane resulted in pronounced reduction of intention tremor assessed by magnetic tracking of grasping movements as well as accelerometer total power measuring high-amplitude batwing tremor. The mean coordinates of the most effective contacts (right: 12.9 ± 1.6, −7.4 ± 1.0, −1.6 ± 1.3; left: −12.3 ± 1.2, −7.3 ± 1.7, −2.6 ± 1.1; x, y, z in mm relative to the midcommissural point) suggested stimulation within the subthalamic area, which is corroborated by post hoc correlation with intraoperative microrecordings. Chronaxie values for suppression of tremor (27 ± 14 μs) and induction of ataxia (52 ± 15 μs; P < 0.05) suggested that tremor suppression is caused by modulation of large myelinated fibers. Notably, optimal contacts could not be used for permanent, bilateral stimulation in several instances, because this was associated with side effects, e.g., paresthesias or dysarthria. Whereas the optimal contact was generally chosen for the dominant side (left electrode), contralateral stimulation was performed with less effective contacts located more dorsally. CONCLUSION: For intention tremor, fiber tracks in the subthalamic area (zona incerta, prelemniscal radiation/cerebellothalamic projections, Forel H2) rather than neuronal cell bodies within the ventrolateral thalamus represent an effective target for DBS. Permanent, bilateral stimulation is frequently performed asymmetrically to prevent side effects.