Background: Although intravenous nefopam has been used for opioid-sparing strategy and pain relief, randomized controlled trials (RCTs) have shown inconsistent findings. Methods: We searched core databases, PubMed, EMBASE, and the Cochrane library for RCTs on this research question in December 2022. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated using a random-effects meta-analysis. Results: Of 708 studies identified from the databases, a total of 17 RCTs (n=1,173 patients) that met the inclusion criteria were included in the final meta-analysis. Overall, the consumption of cumulative opioid analgesics was significantly lower in the nefopam group than the control group, on arrival in the postanesthesia care unit (PACU) (SMD, −0.70; 95% confidence interval [CI], −1.01 to −0.39; I2= 55.1%; n=7), at 24 hours (SMD, −0.65; 95% CI, −1.09 to −0.20; I2=87.4%; n=9), and 48 hours (SMD, −0.82; 95% CI, −1.40 to −0.24; I2=85.6%; n=6) after surgery. It also showed a significant lower pain score, on arrival in the PACU (WMD, −0.80; 95% CI, −1.27 to −0.32; I2=69.6%; n=7) and 24 hours (WMD, −0.48; 95% CI, −0.79 to −0.16; I2=0.0%, n=5). However, publication bias was observed (asymmetrical funnel plot and P for bias=0.005). Conclusions Intravenous nefopam showed an opioid-sparing effect and pain relief in the management of patients with acute postoperative pain.