["Addiction, EarlyView. ", "\nAbstract\n\nBackground and aims\nKratom use in the United States (US) has increased. Kratom is not federally scheduled; regulation is heterogenous and determined at the state level. Strategies include no regulation, bans and kratom consumer protection acts (KCPA) such as age limits, product purity or labeling requirements. Public health data informing these policies remain limited. This study aimed to compare rates of poison center (PC) reported kratom exposures, including those associated with severe medical outcomes and healthcare use, across US states with differing regulatory frameworks, and to characterize national trends in kratom exposures over time.\n\n\nDesign\nRetrospective observational study of kratom exposures reported to the National Poison Data System from 2010 to 2023.\n\n\nSetting\nAll 50 US states and the District of Columbia.\n\n\nParticipants\nA total of 8919 kratom‐related exposures were reported to PCs during the study period, including 5452 single‐substance exposures (61%). Most cases involved adult males (69%), aged ≥18 years (8133; 91%).\n\n\nMeasurements\nStates were classified by kratom regulatory status into four categories: unrestricted (no regulations), KCPA, local restrictions (KCPA in 1 or more county, but no state regulation) or banned (retail sale illegal). The primary outcome was the incidence of severe medical outcomes defined as exposures coded by America's Poison Centers criteria as major effect (life‐threatening or resulting in significant residual disability) or death. Secondary outcomes included rates of exposure, hospitalization and healthcare use (defined as hospital admission or evaluation in an emergency department, urgent care or primary care).\n\n\nFindings\nKratom exposures increased from 19 cases in 2010 to 1242 cases in 2023 [incidence rate ratio (IRR) = 69.0 compared with 2010; 95% confidence interval (CI) = 39.6–120; P < 0.001]. Severe medical outcomes increased from zero cases in 2010 to 158 cases in 2023; 2012 was the first year in which a severe outcome was reported (2023 IRR = 56.9 vs 2012; 95% CI = 14.7–221; P < 0.001). Overall, 13% of kratom exposures resulted in a severe medical outcome. Compared with states where kratom was banned, statistically significantly higher rates of exposures (IRR = 2.49; 95% CI = 1.89–3.28), severe medical outcomes (IRR = 3.19; 95% CI = 1.78–5.70), healthcare use (IRR = 2.44; 95% CI = 1.66–3.60) and hospitalization (IRR = 2.45; 95% CI = 1.81–3.30, P < 0.001) occurred (all P < 0.001). No statistically significant differences were identified between other regulatory categories.\n\n\nConclusion\nKratom exposures and severe medical outcomes reported to United States poison centers are increasing nationally, though states with bans in place have experienced less pronounced increases.\n\n"]