OBJECTIVESTo assess the feasibility and clinical efficacy of local field potentials (LFPs)–based adaptive deep brain stimulation (aDBS) in patients with advanced Parkinson disease (PD) during daily activities in an open-label, nonblinded study. METHODSWe monitored neurophysiologic and clinical fluctuations during 2 perioperative experimental sessions lasting for up to 8 hours. On the first day, the patient took his/her daily medication, while on the second, he/she additionally underwent subthalamic nucleus aDBS driven by LFPs beta band power. RESULTSThe beta band power correlated in both experimental sessions with the patientʼs clinical state (Pearson correlation coefficient r = 0.506, p < 0.001, and r = 0.477, p < 0.001). aDBS after LFP changes was effective (30% improvement without medication 3-way analysis of variance, interaction day × medication p = 0.036; 30.5 ± 3.4 vs 22.2 ± 3.3, p = 0.003), safe, and well tolerated in patients performing regular daily activities and taking additional dopaminergic medication. aDBS was able to decrease DBS amplitude during motor “on” states compared to “off” states (paired t test p = 0.046), and this automatic adjustment of STN-DBS prevented dyskinesias. CONCLUSIONSThe main findings of our study are that aDBS is technically feasible in everyday life and provides a safe, well-tolerated, and effective treatment method for the management of clinical fluctuations. CLASSIFICATION OF EVIDENCEThis study provides Class IV evidence that for patients with advanced PD, aDBS is safe, well tolerated, and effective in controlling PD motor symptoms.