ImportanceA key objective in contemporary surgery is to reduce or eliminate the usage of opioids to minimize gastrointestinal adverse effects, fatigue, and long-term opioid dependency.ObjectivesTo evaluate the association of the implementation of a care bundle of 3 opioid-sparing interventions with the amount of opioids consumed postoperatively among patients undergoing major abdominal surgery and to examine the respective associations of the 3 components.Design, Setting, and ParticipantsThis retrospective cohort study was performed at Ersta Hospital, an elective teaching hospital in Stockholm, Sweden. All patients undergoing major colorectal surgery between January 1, 2016, through December 31, 2019, were included. Data analysis was conducted from February 1, 2020, to May 30, 2022.ExposuresA care bundle consisting of an individualized opioid regimen, regular gabapentinoids, and clonidine as a rescue analgesic was gradually introduced early in the study period.Main Outcomes and MeasuresAmount of in-hospital administered intravenous and oral opioids on the day of surgery and the first 5 postoperative days (morphine milligram equivalents [MME]). The association between exposure and outcome was examined using multivariable linear regression.ResultsOverall, 842 patients had major colorectal surgery in the study period (mean [SD] age, 64.6 [15.5] years; 421 [50%] men). Median (range) opioid usage decreased from 75 (0-796) MME in 2016 to 22 (0-362) MME in 2019 (P < .001), and the proportion of patients receiving 45 MME or less increased from 35% to 66% (P < .001). On multivariable analysis (F5, 836 = 57.5; P < .001), an individualized opioid strategy (β = −11.6; SE = 3.8; P = .003), the use of gabapentin (β = −39.1; SE = 4.5; P < .001), and increasing age (β = −1.0; SE = 0.11; P < .001) were associated with less opioid consumption, while the use of clonidine was associated with more opioid intake (β = 11.6; SE = 3.6; P = .001).Conclusions and RelevanceIn this cohort study of 842 patients undergoing colorectal surgery, a care bundle consisting of an individualized opioid regimen, regular gabapentin, and clonidine as a rescue analgesic was found to be associated with a significant decrease in opioids consumed postoperatively. Regular gabapentin and an individualized opioid regimen were particularly strongly associated with this decrease and should be further evaluated as components of multimodal, opioid-free postoperative analgesia.