Background. Survivors of childhood acute myeloid leukemia (AML) face increased risks of chronic disease and secondary malignancies. Substance exposure may compound these risks. Procedures. Participants were diagnosed with AML at <21 years of age and survived ≥5 years following diagnosis. All underwent chemotherapy alone or followed by autologous BMT (chemo ± autoBMT) or underwent allogeneic BMT (alloBMT) if an HLAmatched related donor was available. Survivors completed a health questionnaire and a Youth Risk Behavior Survey (YRBS). Results. Of eligible survivors, 117 were ≥18 years of age and completed a YRBS. Survivors were a mean age of 10 years at diagnosis and 24 years at interview. Of the substance exposures assessed by YRBS, tobacco, alcohol, and marijuana were most common. Twenty-two percent (22%) had smoked cigarettes in the last 30 days. One-quarter (25%) reported binge drinking in the last month. None of these exposures varied by treatment group. Less than 10% of survivors reported cocaine, heroin, or methamphetamine use. Men were more likely to report high substance exposure (P=0.004). Sadness/suicidality score was associated with cancer-related anxiety (P=0.006) and multiple health conditions (P=0.006). Conclusions. This analysis reveals exposure to tobacco, alcohol, and marijuana in young adults with few differences based on treatment received. Survivors with cancer-related anxiety or multiple health conditions were more likely to report sadness/hopelessness.