Background Ultrasound-guided Erector Spinae Plane Block (ESPB) has been increasingly applied in patients for postoperative analgesia. Its safety and effectiveness remain uncertain. This meta-analysis aimed to determine the clinical safety and efficacy of ultrasound-guided ESPB in adults undergoing general anesthesia (GA) surgeries. Methods A systematic databases search was conducted in PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing ESPB with control or placebo. Primary outcome was iv. opioid consumption 24 h after surgery. Standardized mean differences (SMDs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model.Results A total of 11 RCTs consisting of 540 patients were included. Ultrasound -guided ESPB showed a reduction of iv. opioid consumption 24 h after surgery (SMD=-2.15; 95% confidence interval (CI) -2.76 to -1.5,p<0.00001), pain scores at 1st hour (SMD=-0.97;95% CI -1.84 to -0.1,p=0.03) and pain scores at 6th hour (SMD=-0.64,95% CI -1.05 to -0.23,p=0.002), Also, it lessened the number of patients who required postoperative analgesia (RR=0.41,95% CI 0.25 to 0.66,p=0,0002) and time to first rescue analgesia (SMD=4.56,95% CI 1.89 to 7.22, p=0.0008). Differences were not significant with the pain score at 12th hour,24th hour and postoperative nausea and vomiting (PONV). Conclusions Ultrasound-guided ESPB provides postoperative analgesic efficacy in adults undergoing GA surgeries with no increase in PONV.