Abstract Purpose To describe secular trends in suicidal thoughts and attempts and the types of health-risk behaviors associated with suicidal thoughts and attempts among U.S. high school students. Methods Data were analyzed from 11 national Youth Risk Behavior Surveys conducted biennially during 1991–2011. Each survey employed a nationally representative sample of students in grades 9–12 and provided data from approximately 14,000 students. Using sex-stratified logistic regression models that controlled for race/ethnicity and grade, we analyzed secular trends in the prevalence of suicidal thoughts and attempts. Adjusted prevalence ratios (APR) were calculated to measure associations between suicide risk and a broad range of health-risk behaviors. Results During 1991–2011, among female students, both suicidal thoughts (seriously considered suicide; made a plan to attempt suicide) and attempts (any attempt; attempt with injury requiring medical treatment) decreased significantly; among male students, only suicidal thoughts decreased significantly. During 2011, compared with students with no suicidal thoughts or attempts, the health-risk behaviors most strongly associated with suicide attempts among female students were injection drug use (APR = 12.8), carrying a weapon on school property (APR = 9.7), and methamphetamine use (APR = 8.7); among male students, the strongest associations were for IDU (APR = 22.4), using vomiting/laxatives for weight control (APR = 17.1), and having been forced to have sex (APR = 14.8). Conclusions School-based suicide prevention programs should consider confidential screening for health-risk behaviors that are strongly associated with suicide attempts to help identify students at increased risk for suicide and provide referrals to suicide and other prevention services (e.g., substance abuse and violence prevention) as appropriate.