Background: This prospective study was conducted for Thalassemic major patients with huge enlargement of spleen attending Azadi-teaching hospital in Kirkuk city during (January 2008- December 2011) on 53 cases (48males and 5 females with mean age 13.3 years; operated on selective basis by open splenectomy through midline or left subcostal incision. Objective: To determine the role of splenectomy in reducing postoperative blood requirement, the efficacy of prophylactic vaccination and post operative penicillin in reducing the incidence of post-splenectomy infection. Methods: Patients with ages <5 years were excluded as with associated other disorders. Results: (81.2%) of the patients were below 10 years old, male preponderance (90.6%), abdominal mass were founded in all patients. Preoperative Hb below 10gm/dl (90.6%), Left sub-costal incision done in (84.9%).Postoperatively, all the patients had an Hb above (8gm/dl.) Seven patients (13.2%) suffered from recurrent URTIs during follow-up. Conclusion: Splenectomy reduced blood requirements, Left sub-costal incision offers good exposure, prophylactic vaccination definitely needs to prevent postoperative infection.