Background <p>Human T-cell lymphotropic virus type 1 (HTLV-1) is a globally prevalent retrovirus associated with adult T-cell leukemia-lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Despite substantial research, the high mortality risk among HTLV-1 carriers remains poorly understood.</p> Objective <p>This study aimed to identify primary causes of hospital admission, predictors of mortality, and long-term survival outcomes in HTLV-1-infected patients.</p> Methods <p>A retrospective cohort study was conducted in two referral hospitals in Mashhad, Iran, from 2011 to 2022, including 308 adult HTLV-1-infected patients. Hospital admissions, clinical outcomes, and mortality predictors were analyzed. Survival analysis was performed on 95 patients who completed follow-up.</p> Results <p>Among the 308 patients, a total of 582 hospital admissions were evaluated. The median age of the patients was 55 years, and 61.4% were female. The primary causes of hospitalization were infectious complications (23.7%), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) (14.8%), and adult T-cell leukemia (ATL) (12.5%). The in-hospital mortality rate was 16.8%, with 98 patients succumbing during their hospital stay. Among patients discharged from the hospital, the median post-discharge survival was approximately 33 months. Factors significantly associated with in-hospital mortality included extended hospital stays, elevated leukocyte counts, high percentages of polymorphonuclear cells, thrombocytopenia, and co-infection with hepatitis B.</p> Conclusion <p>HTLV-1 infection is associated with high mortality during hospitalization and limited long-term survival after discharge, largely driven by infectious complications and co-infections such as hepatitis B. The substantial post-discharge mortality emphasizes the need for improved patient management and robust follow-up care to mitigate long-term mortality risk in this population.</p> Clinical trial number <p>Not applicable.</p>