Background: We tried to understand the prognosis of sickle cell diseases (SCD) in both genders. Methods: All cases with the SCD in the absence of smoking and alcohol were included. Results: The study included 368 patients (168 males and 200 females). Mean age (29.4 versus 30.2 years), associated thalassemia minors (72.0% versus 69.0%), and body mass index (BMI) (21.7 versus 21.6 kg/m2) were similar in males and females, respectively (p>0.05 for all). Whereas total bilirubin value of the plasma (5.2 versus 4.0 mg/dL, p=0.011), transfused units of red blood cells (RBC) in their lives (46.8 versus 29.2, p=0.002), disseminated teeth losses (4.7% versus 1.0%, p<0.001), chronic obstructive pulmonary disease (COPD) (20.8% versus 6.0%, p<0.001), ileus (5.3% versus 2.0%, p<0.01), cirrhosis (5.9% versus 1.5%, p<0.001), leg ulcers (16.0% versus 7.5%, p<0.001), digital clubbing (13.0% versus 5.5%, p<0.001), and chronic renal disease (CRD) (10.7% versus 6.5%, p<0.05) were all higher in males, significantly. Conclusion: SCD are severe inflammatory processes on vascular endothelium, particularly at the capillary level since the capillary system is the main distributor of the hardened RBC into tissues. Although the similar mean age, associated thalassemia minors, and BMI and absence of smoking and alcohol, the higher total bilirubin value of the plasma, transfused units of RBC in their lives, disseminated teeth losses, COPD, ileus, cirrhosis, leg ulcers, digital clubbing, and CRD in males may be explained by the dominant role of male sex in life according to the physical power that may accelerate systemic atherosclerotic process all over the body. Key words: Sickle cell diseases, male sex, chronic endothelial damage, atherosclerosis, metabolic syndrome, early aging, premature death