Background: Anemia in patients with splenomegaly reduces functional ability/capacity and impairs activities of daily living (ADL), which lowers the patient's quality of life and raises their mortality risks. Aim of study: Assessing the impact of high-intensity interval training (HIIT) on functional ability/capacity in splenomegaly anemic patients. Setting: Hematology Unit, Department of Internal Medicine, Cairo University Hospitals (Al-Kasr Al Aini). Design: This randomized controlled HIIT trial was conducted on 50 anemic men with splenomegaly. Subjects: Fifty men suffering from splenomegaly-induced anemia, with ages ranging from 30 to 45 years old, were included. Patients were randomly and equally assigned into 2 groups: a control group and a study group, n = 25 patients for each group. The control group received their medications for 14 weeks in addition to a well-balanced diet, while the study group received the same treatment protocol as the control group in addition to HIIT on a bicycle ergometer three times per week with a total duration of 30-40 minutes per session. Tools: Before and after 14 weeks, a six-minute walk test (6MWT; as a measure for patients' functional capacity), red blood cells (RBCs), hemoglobin (Hb), and Katz Index of Independence in ADL were assessed. Results: Within-group comparison of outcomes showed a significant improvement in the RBCs, Hb, 6MWT, and Katz Index of Independence in both groups but the improvements within the study group were higher than the control group. Between-group comparison of post-values of outcomes showed a significant improvement in the assessed outcomes in the direction of the study group. Conclusion: It could be concluded from this trial that HIIT safely improves functional capacity, RBCS, Hb, and performance of ADL in anemic patients with splenomegaly. Recommendations: It is recommended to incorporate HIIT on a bicycle ergometer three times weekly for 30-40 minutes per session in the treatment protocol for anemic patients with splenomegaly.