Affect regulation is central to multiple theoretical models that explain cannabis use (CU) behavior. However, much of the research has been conducted with adults, leaving unanswered questions about the nature of associations among adolescents, especially those with affective disorders. Using clinical interviews and ecological momentary assessment (EMA), we assessed rates of adolescent CU and momentary associations with affect following psychiatric discharge among youth hospitalized for suicidal thoughts and behaviors. Participants were 13- to 18-year-olds (N = 62; 64.5% female) recruited from an inpatient psychiatric hospital who reported having ever used cannabis. Participants completed clinical interviews during hospitalization. EMA was conducted for 21 days upon discharge. Concurrent use of other drugs was associated with greater odds of CU (odds ratio = 27.63). Momentary CU was associated with higher levels of positive affect and lower levels of anger/irritability, but not with negative affect. The effect of momentary CU on positive affect was greater among youth with a diagnosis of posttraumatic stress disorder (PTSD) or generalized anxiety disorder (GAD). Findings suggest that adolescents may use cannabis to enhance positive emotion, especially those with PTSD/GAD. Results highlight the importance of tailored interventions that focus on providing alternative and adaptive methods to enhance positive affect.