Background: There are many parameters that modulate the severity of sickle cell anemia. Fetal hemoglobin (Hb F) is one of these major variables. However, its effect is clinically inconsistent. We conducted a descriptive study to assess the influence of Hb F on clinical events and hematological variables in patients with sickle cell anemia. Methods: 151 patients with sickle cell anemia with a stable condition, aged 1-18 years, were recruited from March through November 2010. The results of complete blood count and Hb F level and various clinical variables were recorded. Results: Of the 151 patients, the Hb F was more than 20%, 10-20%, and less than 10% in 77 (51%), 60 (39.7%), and 14 (9.3%) patients. A significant negative association was reported between Hb F level and frequency of painful crisis (95% CI=0.05-0.96, OR=0.22), acute chest syndrome (95% CI=0.01-0.43, OR=0.07) and frequency of hospitalizations (95% CI=0.03-0.85, OR=0.11). There was a significant positive association between hemoglobin level (95% CI=2.14-27.17, OR=7.63) and splenomegaly (95% CI=1.37-57.4, OR=12.88) with Hb F level. Conclusion: In children and adolescents with sickle cell anemia, the higher the Hb F levels, the lesser clinical complications of the disease would be. Therefore, patients with low Hb F need close follow-up and monitoring since early age to detect complications as early as possible and consider use of disease modifying agents.