Thoracic paravertebral block is the preferred regional anesthetic technique for breast cancer surgery, but concerns over its invasiveness and risks have prompted search for alternatives. Pectoralis-II block is a promising analgesic technique and potential alternative to paravertebral block, but evidence of its absolute and relative effectiveness versus systemic analgesia (Control) and paravertebral block, respectively, is conflicting. This meta-analysis evaluates the analgesic effectiveness of Pectoralis-II versus Control and paravertebral block for breast cancer surgery.Databases were searched for breast cancer surgery trials comparing Pectoralis-II with Control or paravertebral block. Postoperative oral morphine consumption and difference in area under curve for pooled rest pain scores more than 24 h were designated as coprimary outcomes. Opioid-related side effects, effects on long-term outcomes, such as chronic pain and opioid dependence, were also examined. Results were pooled using random-effects modeling.Fourteen randomized trials (887 patients) were analyzed. Compared with Control, Pectoralis-II provided clinically important reductions in 24-h morphine consumption (at least 30.0 mg), by a weighted mean difference [95% CI] of -30.5 mg [-42.2, -18.8] (P < 0.00001), and in rest pain area under the curve more than 24 h, by -4.7cm · h [-5.1, -4.2] or -1.2cm [-1.3, -1.1] per measurement. Compared with paravertebral block, Pectoralis-II was not statistically worse (not different) for 24-h morphine consumption, and not clinically worse for rest pain area under curve more than 24 h. No differences were observed in opioid-related side effects or any other outcomes.We found that Pectoralis-II reduces pain intensity and morphine consumption during the first 24 h postoperatively when compared with systemic analgesia alone; and it also offers analgesic benefits noninferior to those of paravertebral block after breast cancer surgery. Evidence supports incorporating Pectoralis-II into multimodal analgesia and also using it as a paravertebral block alternative in this population.