Importance Opioid withdrawal involves sympathetic hyperactivity and reduced parasympathetic tone, which standard pharmacological treatments may not adequately address, contributing to relapse vulnerability. Objective To evaluate yoga as adjuvant therapy to accelerate opioid withdrawal recovery and assess its impact on heart rate variability, anxiety, sleep, and pain. Design, Setting, and Participants This 2-arm, early-stage randomized clinical trial was conducted at an addiction medicine inpatient ward in India from April 30, 2023 to March 31, 2024. The outcome assessors and data analyst were blinded to group allocation. Participants included adults aged 18 to 50 years with opioid use disorder experiencing mild to moderate withdrawal symptoms (Clinical Opiate Withdrawal Scale [COWS] scores 4-24). Exclusion criteria included severe withdrawal, neurological conditions affecting autonomic function, severe psychiatric conditions, and recent yoga training. Of 68 individuals screened, 59 were randomized (30 yoga and 29 control participants). Intervention Participants in the yoga group received 10 supervised 45-minute sessions during 14 days alongside standard buprenorphine treatment, including relaxation practices, postures, breathing techniques, and guided relaxation. Participants in the control group received standard buprenorphine treatment only. Main Outcomes and Measures Co–primary outcomes included time to withdrawal stabilization (COWS score &lt;4) and heart rate variability parameters. Secondary outcomes included anxiety (Hamilton Anxiety Rating Scale), sleep latency, and pain scores. Assessments were conducted at baseline (day 1) and day 15. Results Fifty-nine participants (59 male [100%]; mean [SD] age, 25.6 [3.9] years) completed intent-to-treat analysis. Participants in the yoga group recovered faster than those in the control group (hazard ratio [HR], 4.40; 95% CI, 2.40-8.07; P &lt; .001), with a median stabilization time of 5 days (95% CI, 4-6 days) for those in the yoga group vs 9 days (95% CI, 7-13 days) for the control group. Participants in the yoga group showed superior heart rate variability improvements with large effects on low frequency (LF) power (ω 2 = 0.16), high frequency (HF) power (ω 2 = 0.14), and LF/HF ratio (ω 2 = 0.12); all effects were statistically significant ( P &lt; .001). Mediation analysis showed that increases in parasympathetic activity accounted for 23% of the treatment effect (indirect HR, 1.38; 95% CI, 1.10-2.03). Anxiety reduction was significantly greater among those in the yoga group (ω 2 = 0.28; P &lt; .001), with moderate improvements in sleep latency (a 61-minute reduction; P = .008) and pain ( P = .004). Conclusions and Relevance In this randomized clinical trial, yoga significantly accelerated opioid withdrawal recovery and improved autonomic regulation, anxiety, sleep, and pain. These findings support integrating yoga into withdrawal protocols as a neurobiologically informed intervention addressing core regulatory processes beyond symptom management. Trial Registration Clinical Trials Registry of India Identifier: CTRI/2023/04/051302