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Objective: The Enhanced Recovery after Surgery Cardiac Society recommends using multimodal analgesia (MMA) for postoperative pain however, evidence-based guidelines have yet to be established. This study examines the impact of a standardized postoperative MMA pathway in reducing opioid consumption and related complications after cardiothoracic surgery (CTS)., Methods: Within a multicenter healthcare system, a postoperative MMA pathway was developed and implemented at two CTS intensive care units (ICU) while the other CTS ICU opted to maintain the existing opioid-based pathway. A retrospective chart review was conducted on patients admitted to a CTS ICU within this healthcare system after conventional coronary artery bypass grafting and/or valve surgery from September 1, 2018, to June 30, 2019. Comparative analysis was conducted on patients prescribed MMA versus those managed with an opioid-based pathway. The primary outcome was total opioid consumption, converted to morphine milligram equivalents, 72-h post-surgery. Secondary outcomes included mobility within one-day post-surgery, ICU length of stay (LOS), time to first bowel movement (BM), and time to first zero Richmond Agitation-Sedation Scale (RASS)., Results: Seven hundred sixty-two adults were included for final analysis. The MMA group had a higher body mass index, higher percentage of females, were more likely classified as African American and had higher scores for risk-adjusted complications. General Linear Model analysis revealed higher opioid consumption in the MMA group (Est. 0.22, p < 0.0009); however, this was not statistically significant after adjusting for differences in fentanyl usage. The MMA group was more likely to have mobility within one-day post-surgery (OR 0.44, p < 0.0001), have longer time to first BM (OR 1.93, p = 0.0011), and longer time to first zero RASS (OR 1.62, p = 0.0071). The analgesia groups were not a predictor for ICU LOS., Conclusions: Opioid consumption was not reduced secondary to this postoperative MMA pathway. The MMA group was more likely to have mobility within one-day post-surgery. Patients in the MMA group were also more likely to have prolonged time to first BM and first zero RASS. Development and evaluation of a perioperative MMA pathway should be considered., (© 2022. The Author(s).)