To identify factors that affect manifestations of sickle cell anemia we compared patients 11-30 years of age from University of Ibadan, Nigeria (n = 214) and University of Illinois at Chicago, USA (n = 209). Paralleling findings in the general populations of the two countries, the Chicago patients were more often overweight or obese as defined by the Centers for Disease Control (Atlanta, GA, USA) guidelines, and more often had elevated blood pressure (BP) as defined by the National Heart, Lung, and Blood Institute (Bethesda, MD, USA) guidelines. The Ibadan sickle cell anemia patients less frequently received the pneumococcal vaccine or hydroxyurea (HU) therapy. Consistent with lower rates of elevated BP and increased body mass index (BMI), stroke history was less frequent in the Ibadan patients ≥18 years old. Furthermore, in combined analyses, systolic and diastolic BP directly correlated with BMI, and elevated weight status independently associated with history of stroke [odds ratio (OR) 2.7, p = 0.019]. Our findings are consistent with the possibility that higher values for BMI and BP in Chicago sickle cell anemia patients may contribute to an increased risk of stroke and highlights the need for measures to reduce these risk factors. On the other hand, lower pneumococcal vaccination and HU therapy rates in Ibadan patients highlights the need for more improved vaccination coverage and for studies to define the role of HU therapy in Africa.