Role of Opioid-Free Anesthesia Versus Opioid-Based Anesthesia in Postoperative Pain and Opioid Consumption: A Systematic Review and Meta-Analysis

Background/Objectives: Opioid-free anesthesia (OFA) has emerged as a potential alternative to opioid-based anesthesia (OBA) to reduce opioid-related adverse effects. This meta-analysis compares OFA and OBA with respect to postoperative pain and opioid consumption. Methods: PubMed, Cochrane, and Embase libraries were searched for OFA studies published through 12 June 2025. Randomized controlled trials (RCTs) conducted on adult humans were selected; observational studies, studies including neuraxial anesthesia, and RCTs currently awaiting approval were excluded. A forest plot was used to summarize findings of a random-effects meta-analysis to compare OFA (treatment) and OBA (control). Results: Of 1446 citations found, twenty-nine articles met our inclusion criteria. Twenty-six studies reported pain scores with a 0–10 scale. OFA was associated with lower postoperative pain scores (Hedges’ g = –0.34; 95% CI –0.55 to –0.13; p < 0.001; I2 = 84%) but with high heterogeneity, limiting clinical significance or strong interpretation of results. Eleven trials were analyzed for opioid use, showing a small reduction with OFA (Hedges’ g = –0.55; 95% CI –1.10 to –0.005; p = 0.048; I2 = 96.22%). Subgroup outcomes favored OFA, with an overall reduction in pain found specifically in endoscopic abdominal surgeries. Some secondary outcomes also indicated potential improved recovery profiles through OFA for certain surgeries. Conclusions: OFA was associated with statistically significant lower postoperative pain scores, along with opioid consumption, but with a small effect size and high heterogeneity when compared to OBA. This is potentially comparable in pain control and opioid consumption with limited clinical significance. Overall, outcomes support the continued controlled study of OFA as an alternative to conventional analgesia.