Individuals with multiple suicide attempts have a greater risk for eventual suicide death. We investigated clinical differences in participants with single versus multiple suicide attempts. Individuals with multiple attempts were more likely to have severe depressive symptoms, drug use disorder, and a higher wish to die. Borderline personality disorder traits and drug use disorder were significant predictors of multiple attempts when adjusting for other psychiatric disorders. Participants with multiple attempts sustained higher suicidal ideation–worst and wish to die/wish to live–worst scores during the 3-month assessment period. Clinical differences between individuals with multiple versus single attempts point to the need of tailored suicide prevention efforts.