Study Objective Pain management plays a pivotal role in enhanced recovery after surgery (ERAS). Erector spinae plane block (ESPB) is widely used in many regions to treat perioperative pain, but its benefits are still somewhat controversial. We, therefore, intent to systematically review the available literature on ESPB, to elucidate its effects on opioid-sparing analgesia, and summarize its potential complications. Design Systematic review of randomized controlled trials (RCTs) with meta-analysis. Setting Postoperative opioid consumption for various surgeries. Patients Patients undergoing various surgeries. Intervention We searched relevant studies in PubMed, EMBASE, Medline, and the Cochrane Library up to May 16, 2021. All prospective and RCTs that compared ESPB and sham block or no block were enrolled. Measurements The primary outcomes were postoperative opioid consumption during the first 24 hours. The secondary outcomes were the requirement of rescue analgesia, time to first rescue analgesic and ESPB-related adverse events. Results We included 52 trials that reported postoperative opioid consumption during the first 24 hours. The results presented that compared to control group (ie, no intervention or a sham block), ESPB reduced the accumulated opioid consumption during the first 24 h after surgery [mean difference (MD) of − 12.83 (95% CI: − 17.29 to − 8.38; p < 0.001) mg; I 2 = 100%]. Besides, ESPB could prolong time to first rescue analgesia after surgery [SMD = 5.31; 95% CI 4.01–6.61; p < 0.001; I 2 = 97%]. The number of patients who received rescue analgesia after surgery in the ESPB group was less than that in the control group (OR 0.13; 95% CI 0.09, 0.21; p < 0.001; I 2 = 54%), and the incidence of PONV was lower in the ESPB group (OR 0.51; 95% CI 0.43, 0.62; p < 0.001; I 2 = 19%). Conclusion ESPB is an effective technique on pain management with few complications.