Background: Prior research identifies both the physical and psychological effects of cancer treatments as significant predictors of substance use among AYA. However, the prevalence of substance use and its effect on QOL and psychological well-being of AYA hematologic survivors has not been described. Methods: AYA patients (15-40 years at diagnosis) of acute leukemia, aggressive non-Hodgkin lymphoma, Hodgkin lymphoma undergoing curative intent therapy (on-treatment cohort) or 2 year completion of therapy and in remission (early survivor cohort) completed following measures: depression (CES-D), state anxiety (STAI-S), PTSD (PCL-C), QOL (FACIT-G). Semi-structured interviews evaluated substance use. Results: 62 AYA (26 on-treatment, 36 early survivors) were interviewed. For total population: median age at dx 26y (15-40); 64% male; 59% Ca; 79% college/post educ; 41% income <$75,000y; 52% and 48% lymphoma/ leukemia dx, respectively. Overall, 52% AYA reported the current use of a substance (ex. alcohol, nicotine, illicit drug). Of these, 49% AYA reported alcohol use; 20% reported nicotine use; 31% reported illicit drug use (ex. marijuana). AYA who used alcohol had poorer QOL (79±15 v 84±18,p=.02). AYA who used nicotine had higher STAI-S anxiety (44±13 v33±10, p=.01) and CES-D depression (30±16 v 15±8,p<.00). Nicotine use was associated with severe illness-related PTSD symptoms (57±26 v 28±10, p<.00). Also, AYA with illicit drugs use had greater CES-D (20±13 v 11±9, p=.03) and moderate PTSD (41±18 v 29±12, p=.01). On-treatment AYA were more likely to deny current use of illicit drugs (58% v 41%, p=.02) than early survivors. Conclusions: AYAs with hematologic malignancies report substance use negatively impacting QOL thus warranting the need for future age-specific psychological interventions.