The safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients who have had a previous unilateral pallidotomy is not clear. We identified 10 patients (9 male) at the Baylor College of Medicine Parkinson's Disease Center who underwent STN DBS after prior unilateral pallidotomy. Demographics, efficacy as determined by off Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, and levodopa equivalent dosing were analyzed. We then compared these to an age- and sex-matched group of 25 DBS patients who had no prior pallidotomy. After their initial pallidotomy (mean age, 51.8 +/- 10.8 years), the mean UPDRS motor off medicine scores improved from 51.3 +/- 14.3 to 34.9 +/- 12.8, and the UPDRS dyskinesia score improved from 1.8 +/- 1.0 to 0.8 +/- 0.7. Their STN DBS off UPDRS motor scores (mean age, 56.0 +/- 10.2 years) improved by 16.0% from 53.1 +/- 9.7 (range, 42-68) to 44.6 +/- 11.1 (range, 25-67). In contrast, the UPDRS off motor scores in a control group of 25 DBS patients improved by 49.9%, from 49.7 +/- 11.1 to 25.7 +/- 18.9, (16.0% vs. 49.9%; P < 0.001). Changes in UPDRS dyskinesia scores were similar in both groups. AE thought to be related to the STN DBS following pallidotomy included worse dysarthria (three) and worse balance (two). STN DBS patients with prior pallidotomy had less improvement in UPDRS off motor score compared to other STN DBS patients, despite relatively good outcomes immediately after their pallidotomy. This may be partially due to a selection bias, but it may also indicate that prior pallidotomy is a negative predictor of outcome of STN DBS and should be considered in patient selection.