Substance use contributes to significant societal burdens, including high-cost health care use. However, these burdens may vary by type of substance and level of involvement. Using the 2009–13 National Surveys on Drug Use and Health, we examined all-cause hospitalizations and estimated costs across substance use profiles for alcohol, marijuana, and other illicit drugs. For each substance, we characterized differences between abstainers, nondiagnostic users (people who used the substance but did not meet diagnostic criteria for substance use disorder), and people with substance use disorders. In a multivariate analysis, we found that the odds of hospitalization were 16 percent lower for nondiagnostic marijuana users and 11 percent lower for nondiagnostic alcohol users, compared to abstainers. Neither alcohol- nor marijuana-specific substance use disorders were associated with hospitalization. In contrast, substance use disorders for other illicit drugs were strongly associated with hospitalization: People with those disorders had 2.2 times higher odds of hospitalization relative to abstainers. A more detailed understanding of health care use in different substance user groups could inform the ongoing expansion of substance use services in the United States.