CONTEXT Sickle cell anemia (SCA) is a group of hemoglobin disorders in which the sickle β-globin gene is inherited. It is associated with many complications; most of them are related to thrombotic events. AIM This study aimed to investigate the association between angiotensin converting enzyme (ACE) insertion/deletion polymorphism and complications of SCA. SETTINGS AND DESIGN A case-control study was conducted in Khartoum state. SUBJECTS AND METHODS A total of 50 patients with SCA and 40 healthy volunteers as a control group were enrolled in this study. Three milliliters of ethylenediamine tetraacetic acid anticoagulated blood were collected from each subject, DNA was extracted by salting-out method, and target DNA regions of the ACE gene were amplified using allele-specific polymerase chain reaction. STATISTICAL ANALYSIS USED Data of this study was analyzed by Statistical Package for Social Sciences. Frequency of qualitative variables was calculated, and correlation was tested by Chi-square test. Regression was used to investigate the association between the polymorphism and complications of SCA. RESULTS The frequencies of the DD, ID, and II genotypes were 42%, 50%, and 8%, respectively, for patients, whereas in the control group, it was 80% for DD genotype and 20% for ID, while II genotype was totally absent. The regression analysis showed no statistically significant association between the disease complications and each of the ACE polymorphic genotypes. CONCLUSION No statistically significant association was found between ACE polymorphism and complications of SCA.