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Gabapentinoids are widely used in perioperative multimodal analgesic regimens. The primary aim of this study was to determine whether gabapentin was associated with respiratory depression during phase-I postanesthesia recovery after major laparoscopic procedures.We retrospectively reviewed the electronic health records of 8567 patients who underwent major laparoscopic procedures (lasting ≥90 minutes) from January 1, 2010, to July 31, 2014. We assessed potential associations among patient and perioperative variables and episodes of respiratory depression during phase-I recovery. Multivariable and propensity score–matched analyses were performed to assess potential associations between preoperative gabapentin use and postoperative respiratory depression.The incidence of respiratory depression was 153 (95% confidence interval [CI], 146–161) episodes per 1000 cases. Multivariable analysis showed that gabapentin was associated with respiratory depression (odds ratio [OR], 1.47 [95% CI, 1.22–1.76]; P < .001). These results were confirmed by propensity score–matched analysis among a subset of patients who did not have analgesia supplemented by intrathecal opioids (OR, 1.26 [95% CI, 1.02–1.58]; P = .04). Older patients and those who received more intraoperative opioids had increased risk of respiratory depression. Those who had an episode of respiratory depression had a longer phase-I recovery (P < .001) and an increased rate of admission to a higher level of care (P = .03).The use of gabapentin is associated with increased rates of respiratory depression among patients undergoing laparoscopic surgery. When gabapentinoids are included in multimodal analgesic regimens, intraoperative opioids must be reduced, and increased vigilance for respiratory depression may be warranted, especially in elderly patients.