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Abstract   Background: Methamphetamine use is associated with numerous adverse physical and mental health outcomes. This study investigated the prevalence and distribution of lifetime methamphetamine use (MU) as well as the association between methamphetamine use and engagement in sexual risk behaviors among a nationally representative sample of U.S. high school students. Methods: A secondary analysis of the 2003 Youth Risk Behavior Survey (n = 15,240) was carried out. Weighted descriptive and logistic regression analyses were conducted to determine the prevalence of MU by socio-demographic characteristics and the association between drug use and sexual risk behaviors. Results: Prevalence of having used methamphetamine ≥1 times (lifetime methamphetamine use) (7.6%; 95%CI  1.0) was comparable to lifetime cocaine use but over double the rate of lifetime heroin use. Males reported slightly higher MU than females (8.3%1.4 vs. 6.8%1.0). MU was more than twice as high for white (8.1%1.1) and Hispanic (8.2%2.2) students compared to black students (3.1%1.0). MU was associated with ∼2 to 11 times the likelihood of engaging in one of the six sexual risk behaviors examined. Heavy methamphetamine users were >4 times more likely to report having had sexual intercourse before age 13, sex with multiple partners, and having been/gotten someone pregnant compared to those who used methamphetamine 1–2 times. Conclusion: Findings indicate that a substantial number of U.S. youth have used methamphetamine, that white and Hispanic high school students may be at higher risk for methamphetamine use, and that methamphetamine users may be at higher risk for engaging in sexual risk behaviors. [ABSTRACT FROM AUTHOR]