Objectives <p>To compare ethanol pharmacokinetics before and after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) over a three-year period.</p> Methods <p>This was a prospective, longitudinal, non-randomized controlled study at St. Olavs Hospital, Trondheim, including 33 adults without histories of alcohol use disorder (RYGB: <i>n</i> = 14; SG: <i>n</i> = 19). Participants underwent oral and intravenous ethanol challenge tests preoperatively and at 3, 12, and 36 months postoperatively. Primary outcomes included maximum plasma concentration (C_max), time to reach maximum concentration (T_max), and area under the curve to the last measurable concentration (AUC_last).</p> Results <p>The ethanol uptake after both surgical procedures was bioequivalent for AUC_last, but not for C_max and T_max. At 12 months, RYGB gave a 27% higher C_max and 31% shorter T_max than SG, while no significant differences were observed for AUC_last. Both procedures induced profound and persistent alterations in ethanol pharmacokinetics over the three-year period: C_max and AUC_last approximately doubled, and T_max was reduced to about half the preoperative value. C_max occurred within 9–15 min compared to 25–29 min before surgery. Patients also had concomitant reductions in total body water, averaging 3.2 kg after SG and 4.8 kg after RYGB at 12 months.</p> Conclusion <p>Both RYGB and SG permanently altered ethanol pharmacokinetics, resulting in faster absorption, higher peak concentrations, and higher systemic exposure of alcohol. These changes, which were more pronounced after RYGB, may increase the risk of alcohol use disorders post-surgery. Awareness of the pharmacokinetic effects on RYGB and SG may be relevant for patient education, surgical decision-making, and postoperative monitoring.</p> Clinical trial registration <p>This study was registered in ClinicalTrials.gov on May 15 2013. Identifier: NCT01840020.</p>