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Pectoralis and serratus blocks have been described recently for use in breast surgery, but evidence supporting their analgesic benefits is limited. This cohort study evaluates the benefits of adding a pectoralis or serratus block to conventional opioid-based analgesia (control) in patients who underwent ambulatory breast cancer surgery at Women’s College Hospital between July 2013 and May 2015. We tested the joint hypothesis that adding a pectoralis or serratus block reduced postoperative in-hospital (predischarge) opioid consumption and nausea and vomiting (PONV). We also examined the 2 block types for noninferiority.A total of 225 patients were propensity matched on 5 potential confounders among 3 study groups (75 per group): (1) pectoralis; (2) serratus; and (3) control. The propensity-matched cohort was used to evaluate the effect of the study group on postoperative in-hospital oral morphine equivalent consumption and PONV. We considered pectoralis noninferior to serratus block if it was noninferior for both outcomes, within 10 mg morphine and 17.5% in PONV incidence margins. Other outcomes included intraoperative fentanyl requirements, pain scores, time to first analgesic request, and duration of recovery room stay.Both pectoralis and serratus blocks were each associated with reduced postoperative in-hospital opioid consumption and PONV compared with control. Pectoralis was noninferior to serratus block for these 2 outcomes. Pectoralis and serratus blocks were each associated with reduced intraoperative fentanyl requirements, prolonged time to first analgesic request, and expedited recovery room discharge compared with control; there were no differences for the remaining outcomes.Pectoralis and serratus blocks were each associated with a reduction in postoperative in-hospital opioid consumption and PONV compared with conventional opioid-based analgesia after ambulatory breast cancer surgery.