BACKGROUNDSplenectomy is frequently performed in transfusion-dependent thalassemia (TDT) patients to lower blood transfusion needs but is associated with significant long-term complications, including sepsis, thrombosis, and pulmonary hypertension. This study examines the long-term complications, survival rates, and causes of mortality among adult patients with TDT who have undergone splenectomy in a low and middle-income country (LMIC).METHODSA retrospective analysis was conducted on 103 adult TDT patients (≥18 years) who underwent splenectomy between July 2013 and March 2024. Data collected included demographic and clinical characteristics, haematological parameters, transfusion requirements before splenectomy and at the last follow-up, survival rates, complications, and mortality causes.RESULTSThe median age at splenectomy was 12 years (range 5-34). The majority (98 %) underwent open splenectomy. The yearly transfusion volume decreased from 276.7 ml/kg/year pre-splenectomy (range 207-433) to 146.2 (range 0-252.9) post-splenectomy at the last follow-up, p < 0.0001. Three patients were completely transfusion-free at the last follow-up. Complications included pulmonary hypertension in 10 (9.7 %), thrombosis in 5 (4.8 %), and overwhelming post-splenectomy infection (OPSI) in 4 (3.9 %). The iron-overload-related complications included cardiomyopathy in 17 (16.5 %), endocrinopathy in 56 (54.3 %), chronic liver disease in 15 (14.5 %) and hepatocellular carcinoma in 2 (0.9 %). The 15-year post-splenectomy overall survival (OS) was 84.7 % (95 % CI- 77.3 % - 92.8 %), with 17 deaths (16.5 %) recorded. Iron-overload-related cardiomyopathy was the leading cause of death in 8 (53.3 %).CONCLUSIONSplenectomy significantly reduces transfusion requirements in TDT patients but is associated with risks such as thrombosis, pulmonary hypertension, and OPSI. Long-term mortality is primarily driven by iron-overload-related cardiomyopathy.