Adolescents with sickle cell disease may have problems of adjustment during the phase of transition from pediatric to adult health care. It is important to identify factors that may help in the development of appropriate interventions. We were interested in possible similarities, in terms of adjustment to transition in two countries where health service provision is quite different. The study employed a cross-sectional survey design, with a sample of adolescents (still in pediatric care) drawn from a U.S.A national sample and a single U.K. site. A battery of validated disease-specific measures was used to assess adolescent perceptions of physical and psychological symptoms, self-efficacy, self-management skills, and gather demographic data. There were no significant demographic differences between the samples of adolescents in the two countries. Taken together, the two populations indicate that adolescent age and educational level were associated with symptoms (physical and psychological). Self-efficacy is not associated with demographic factors, but is predicted by physical symptoms, while different aspects of self-management are predicted by age (responsibility with care), educational level (independence and confidence with care) and psychological symptoms (knowledge about SCD and confidence with care). This study highlights the importance of gathering disease-specific transitional information from adolescents with sickle cell disease in the U.K. and U.S.A. It also shows that demographic variables have to be considered in the development of any intervention programme.