ABSTRACT: INTRODUCTION:National estimates of U.S. Native Hawaiian and other Pacific Islander (NHPI), American Indian/Alaskan Native (AIAN), and multiracial adolescent substance use and suicidality are scarce because of their small population sizes. The aim was to estimate the national prevalence of, and disparities in, substance use and suicidality among these understudied adolescents. METHODS:Analyses conducted in 2017 of U.S. adolescents (grades ninth to 12th) from the 1991-2015 Combined National Youth Behavioral Risk Surveys estimated (1) prevalence of lifetime and current (past 30-day) substance use, past 12-month depressed mood, and suicidality by racial group; and (2) AORs for depressed mood and suicidality regressed on current alcohol, cigarette, and marijuana use. RESULTS:Among 184,494 U.S. adolescents, alcohol, cigarettes, and marijuana were commonly used with lifetime prevalence of 75.32%, 58.11%, and 40.55%, respectively, and current prevalence of 44.51%, 24.58%, and 22.01%, respectively. Past 12-month prevalence of suicidal thoughts, suicide planning, and attempted suicide were 18.87%, 14.75%, and 7.98%, respectively. Relative to non-Hispanic whites, NHPI, AIAN, and multiracial adolescents had higher prevalence of using many illicit substances (e.g., marijuana, heroin), depressed mood, and suicidal thoughts, planning, and attempts (p<0.05). Except for NHPIs and current alcohol use, current alcohol and cigarette use were independently associated with 2.0-2.3 times greater AORs (p<0.05) for attempted suicide among the target adolescents. CONCLUSIONS:U.S. NHPI, AIAN, and multiracial adolescents are disproportionately burdened by illicit substance use, depressed mood, and suicidality. Current alcohol and cigarette use may predispose these adolescents toward suicidality, offering potential pathways to alleviate suicide risk.