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Serratus fascial plane block can reduce pain following breast surgery, but the question of whether to inject the local anesthetic superficial or deep to the serratus muscle has not been answered. This cohort study compares the analgesic benefits of superficial versus deep serratus plane blocks in ambulatory breast cancer surgery patients at Women's College Hospital between February 2014 and December 2016. We tested the joint hypothesis that deep serratus block is noninferior to superficial serratus block for postoperative in-hospital (pre-discharge) opioid consumption and pain severity.One hundred sixty-six patients were propensity matched among 2 groups (83/group): superficial and deep serratus blocks. The cohort was used to evaluate the effect of blocks on postoperative oral morphine equivalent consumption and area under the curve for rest pain scores. We considered deep serratus block to be noninferior to superficial serratus block if it were noninferior for both outcomes, within 15 mg morphine and 4 cm·h units margins. Other outcomes included intraoperative fentanyl requirements, time to first analgesic request, recovery room stay, and incidence of postoperative nausea and vomiting.Deep serratus block was associated with postoperative morphine consumption and pain scores area under the curve that were noninferior to those of the superficial serratus block. Intraoperative fentanyl requirements, time to first analgesic request, recovery room stay, and postoperative nausea and vomiting were not different between blocks.The postoperative in-hospital analgesia associated with deep serratus block is as effective (within an acceptable margin) as superficial serratus block following ambulatory breast cancer surgery. These new findings are important to inform both current clinical practices and future prospective studies.