Background: Recent trends show methamphetamine use is increasing in the United States. American Indian and Alaska Native (AI/AN) communities face health disparities compared to the population overall, including some of the highest rates of illegal drug use. Herein, we examined the prevalence of methamphetamine use among AI/ANs and characteristics associated with methamphetamine use among AI/AN people., Methods: We examined past-year methamphetamine use from 2015 to 2019 between AI/ANs and the general non-institutionalized U.S. population using the National Survey of Drug Use and Health. Then, we identify potential subgroups of AI/AN people at elevated risk of methamphetamine use across factors including demographic, social determinants, mental health, and co-occurring substance use., Results: A total of 214,505 people, aged 18 or older, were surveyed between 2015 and 2019; 3,075 (0.55%) identified as AI/AN. An estimated 26.2 out of every 1000 AI/ANs used methamphetamine compared to 6.8 out of every 1000 in the general U.S., Population: Compared to methamphetamine use in the general population, AI/AN methamphetamine use tends to cluster in rural areas and among those with low income. AI/ANs who use methamphetamine were more likely to be male, middle-aged, low income, have severe mental illness, and misuse other substances than AI/AN people who did not use methamphetamine., Discussion: AI/ANs experience a disproportionate amount of methamphetamine use in the U.S. To address this disparity, multifaceted, broad prevention, harm reduction, and treatment efforts are needed that leverage cultural strengths to mitigate the consequences of methamphetamine use., (Copyright © 2021 Elsevier B.V. All rights reserved.)