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Due to the ongoing medical challenges we hypothesized that older adolescents with sickle cell disease (SCD) would report greater rates of internalizing symptoms and diagnoses. This study is a follow-up to a previous study  that found few differences between the emotional well-being of children ages 8–15 with SCD and comparison peers. Our aim is to re-assess internalizing symptoms of youth with SCD and comparison peers at age 18.At follow-up, trained staff members administered semi-structured psychiatric interviews and widely use behavioral health questionnaires to adolescents with SCD (n = 48), their comparison peers (COMP; n = 51) and a caregiver. Mood, internalizing symptoms and diagnoses, were evaluated cross-sectionally at the follow-up (age 18).Psychiatric interview data showed that COMP reported more phobias relative to adolescents with SCD; no significant differences were reported for any other current symptoms (depression, anxiety, or mania). Questionnaire data showed all scores in the normal range with two significant differences: older adolescents with SCD reported more symptoms of tension-anxiety and fatigue-inertia. Both groups reported significant rates of internalizing disorders with 31% of youth with SCD and 35% of COMP having a DSM-IV diagnosis.Psychiatric interview data for both groups of older adolescents suggested considerable psychopathology; questionnaire data for both groups were in the normal range. We report few significant differences—more phobias in comparisons peers; more tension-anxiety and fatigue-inertia reported by youth with SCD. The overall findings suggest considerable resilience for youth with SCD, but both groups of adolescents report significant rates of psychopathology similar to national rates. Pediatr Blood Cancer 2015;62:637–642. © 2014 Wiley Periodicals, Inc.