Background Pectoral nerve blocks have been proposed for analgesia during and after breast cancer surgery, but data are conflicted in aesthetic breast surgery. This trial tested the primary hypothesis that adding a preincisional pectoral nerve block is superior to systemic multimodal analgesic regimen alone for pain control after breast augmentation surgery. A second hypothesis is that rescue opioid consumption would be decreased with a long-lasting effect for both outcomes during the following days. Methods Seventy-three adult female patients undergoing aesthetic breast augmentation surgery under general anesthesia were randomly allocated to receive a pectoral nerve block versus no block. Both groups received standard care with protocolized multimodal analgesia alone including systematic acetaminophen and nonsteroidal anti-inflammatory drugs. The primary outcome measure was the maximal numerical rating scale in the first 6 h after extubation. Secondary outcomes included intraoperative remifentanil consumption and from extubation to day 5: maximal numerical rating scale, postoperative cumulative opioid consumption and postoperative opioid side effects, and patient satisfaction recorded at day 5. Results The maximal numerical rating scale score in the first 6 h was lower in the pectoral nerve block group compared with the control group (3.9 ± 2.5 vs. 5.2 ± 2.2; difference: –1.2 [95% CI, –2.3 to –0.1]; P = 0.036). The pectoral nerve block group had a lower maximal numerical rating scale between days 1 and 5 (2.2 ± 1.9 vs. 3.2 ± 1.7; P = 0.032). The cumulative amount of overall opioids consumption (oral morphine equivalent) was lower for the pectoral nerve block group from hour 6 to day 1 (0.0 [0.0 to 21.0] vs. 21.0 [0.0 to 31.5] mg, P = 0.006) and from days 1 to 5 (0.0 [0.0 to 21.0] vs. 21.0 [0.0 to 51] mg, P = 0.002). Conclusions Pectoral nerve block in conjunction with multimodal analgesia provides effective perioperative pain relief after aesthetic breast surgery and is associated with reduced opioid consumption over the first 5 postoperative days. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New