The nociception level (NOL) index is a quantitative parameter derived from physiological signals to measure intraoperative nociception. The aim of this systematic review and meta-analysis was to evaluate if NOL monitoring reduces intraoperative opioid use compared to conventional therapy (opioid administered at clinician discretion). This meta-analysis comprises randomized clinical trials comparing NOL-guided opioid administration to conventional therapy in adult patients undergoing any type of surgery. A systematic search of PubMed, Scopus, and CENTRAL databases was conducted. The primary outcome was intraoperative opioid consumption and the effect estimate of the NOL index was measured using the standardized mean difference (SMD) where 0.20 is considered a small and 0.80 a large effect size. A random-effects model with Hartung-Knapp-Sidik-Jonkman adjustment was applied to estimate the treatment effect. Heterogeneity was explored clinically and statistically (using the inconsistency I² statistic, prediction intervals, and influence analysis). The quality (certainty) of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines methodology. This review comprised 9 trials (519 patients). The intraoperative opioid SMD (NOL monitoring versus conventional therapy) was -0.26 (95% confidence interval [CI], -0.82 to 0.30; P = .31; low certainty of evidence). We observed substantial clinical (intraoperative opioid regimens) and statistical heterogeneity with the I² statistic being 86% (95% CI, 75%-92%). The prediction interval was between -1.95 and 1.42 indicating where the SMD between NOL and conventional therapy would lie if a similar study were conducted in the future. This meta-analysis does not provide evidence supporting the role of NOL monitoring in reducing intraoperative opioid consumption.