To assess the prevalence of nocturnal enuresis in children and adolescents with sickle cell disease (SCD) and associated factors, structured telephone interviews were conducted with primary caregivers of 217 children and adolescents with SCD aged 5 years or older. Prevalence, perceived causes, interventions undertaken, and emotional impact were assessed. Nocturnal enuresis was significantly higher for males (28.2% of males) than for females (11% of females),p= .002, and compared with cited population prevalence rates, nocturnal enuresis was significantly higher for children with SCD,p< .01. SCD was the most common reason given by primary caregivers for enuresis. Primary caregivers used a wide range of interventions for nocturnal enuresis, but few used empirically supported treatments for enuresis or spoke with their health care team about the enuresis. These data suggest that systematic assessment and intervention for nocturnal enuresis must be implemented in the follow-up care of children and adolescents with SCD.