Successful management of opioid withdrawal improves long-term treatment outcomes and reduces opioid use-related morbidity and mortality. Mechanistically supported pharmacotherapeutic approaches are needed to effectively manage acute and protracted opioid withdrawal. Buspirone is a D2 antagonist and 5-HT1a agonist that may decrease opioid withdrawal. Individuals (n = 15) admitted to a residential treatment center for opioid use disorder (OUD) were enrolled into a double-blind randomized clinical trial to assess the efficacy and acceptability of buspirone (45 mg/day) as an adjunctive medication to buprenorphine-assisted, supervised opioid withdrawal. Participants completed daily questionnaires which consisted of the Subjective Opiate Withdrawal Scale (SOWS) and a consensus sleep diary, which assessed total sleep time, time to sleep onset, and sleep quality. Total SOWS scores, individual opioid withdrawal symptoms and sleep outcomes were assessed between treatment groups (Placebo and Buspirone) and over time in a repeated measures linear mixed model. Total SOWS scores significantly decreased across study phases for both groups but decreased to a greater extent among individuals assigned to buspirone during both the first and second week of stable buspirone. Greater decreases in withdrawal were observed during Week 2 of stable buspirone relative to Week 1 of stable buspirone. Participants also reported significant increases in sleep duration and significant decreases in latency to sleep onset. This study provides further support that buspirone can help mitigate opioid withdrawal during a supervised opioid taper. Buspirone may confer unique benefits during protracted withdrawal periods. (PsycInfo Database Record (c) 2023 APA, all rights reserved).