Sickle cell disease is a major cause of maternal and neonatal mortality in tropical regions. Treatment consists of regular blood transfusion during pregnancy and delivery. Transfusion may be performed selectively (in function of the clinical status of the mother, fetus, and pregnancy) or prophylactically. Both management strategies result in a significant improvement in the obstetric outcome. However systematic prophylactic transfusion has been shunned due to the risk of transmitting infections and allo-immunization. The16-case series reported here demonstrates a real benefit for prophylactic blood transfusion during pregnancy complicated by sickle cell disease in tropical zones. Improvements in our transfusion curves resulting from better donor selection, follow-up, and phenotyping support arguments previously made over one decade ago in favor of the prophylactic approach especially in countries with high transfusional risks. In our experience the risks associated with more transfusions was offset by the greater safety margin and better efficacy of the prophylactic approach.