OBJECTIVE: To obtain patient perspectives on (1) factors important in SCD-related HrQoL and (2) current impediments to QoL. METHODS: Four semi-structured focus groups were conducted with African American sickle cell disease (SCD) patients, 21-26 years old. Subjects were recruited from a tertiary care academic center or a community setting. Inductive analysis of verbatim transcripts assisted with computer software resulted in over 200 codes grouped into five themes: illness experience, health care system, social networks, life stages/transition, and community/society. RESULTS: Young adults with SCD faced similar issues as those with other chronic health conditions: greater responsibility associated with autonomy and difficulty developing relationships with unfamiliar providers. Patients also faced challenges unique to SCD. The unpredictability of SCD and its associated multi-organ system complications implies recurrent illness and pain episodes, requiring a greater focus on acute medical events rather than on chronic health maintenance. Furthermore, SCD heterogeneity, both between patients and within each individual, resulted in difficulty predicting disease course, limiting the attainment of occupational and educational goals. Patient autonomy was often undermined by a need to rely on social support systems during acute illness. Patients contended with health care provider misperceptions, e.g., underestimation of their pain severity based upon outward appearance; being labeled as "drug-seeking" when notifying providers of successful pain strategies. Patient frustration with lack of access to SCD specialists in the community setting was confounded by a lack of public awareness of SCD-related issues. Informants also described economic challenges and faced limitations imposed by reliance on governmental assistance, such as fewer providers, limited coverage, loss of benefits with employment and difficulty obtaining health insurance due to preexisting illness. CONCLUSIONS: The impact of SCD far exceeds the clinical manifestations of the illness. Patients are faced with life interruptions, social limitations, and physical challenges that impede functioning in an uninhibited society.