Anxiety disorders affect ~ 15-20% of youths without neurodevelopmental disorders, with persons having autism spectrum disorder (ASD) and fragile X syndrome (FXS) at elevated risk for anxiety disorders. Few studies have compared rates and predictors of anxiety disorders in adolescents with FXS or ASD. This study directly compares rates, predictors, and medication of anxiety disorders between age-matched, male adolescents with FXS (n = 31) or ASD (n = 20). Results indicate that 51.6% of FXS and 50.0% of ASD adolescents met criteria for an anxiety disorder. Cognitive scores and ASD severity did not predict anxiety. Of those with anxiety, ~ 40% of the FXS and 20% of the ASD participants were prescribed medications for anxiety.