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To evaluate whether a liposomal bupivacaine incisional block decreases postoperative pain and represents an opioid-minimizing strategy after scheduled cesarean delivery.In a single-blind, randomized controlled trial among opioid-naive women undergoing cesarean delivery, liposomal bupivacaine or placebo was infiltrated into the fascia and skin at the surgical site, before fascial closure. Using an 11-point numeric rating scale, the primary outcome was pain score with movement at 48 hours postoperatively. A sample size of 40 women per group was needed to detect a 1.5-point reduction in pain score in the intervention group. Pain scores and opioid consumption, in oral morphine milligram equivalents, at 48 hours postoperatively were summarized as medians (interquartile range) and compared using the Wilcoxon rank-sum test.Between March and September 2017, 249 women were screened, 103 women enrolled, and 80 women were randomized. One woman in the liposomal bupivacaine group was excluded after randomization as a result of a vertical skin incision, leaving 39 patients in the liposomal bupivacaine group and 40 in the placebo group. Baseline characteristics between groups were similar. The median (interquartile range) pain score with movement at 48 hours postoperatively was 4 (2–5) in the liposomal bupivacaine group and 3.5 (2–5.5) in the placebo group (P=.72). The median (interquartile range) opioid use was 37.5 (7.5–60) morphine milligram equivalents in the liposomal bupivacaine group and 37.5 (15–75) morphine milligram equivalents in the placebo group during the first 48 hours postoperatively (P=.44).Compared with placebo, a liposomal bupivacaine incisional block at the time of cesarean delivery resulted in similar postoperative pain scores in the first 48 hours postoperatively.ClinicalTrials.gov, NCT02959996.