OBJECTIVES: Myelodysplastic syndromes (MDS) are a group of malignant hematologic diseases characterized by ineffective bone marrow hematopoiesis, with up to 30% of patients progressing to acute myeloid leukemia (AML). Associated anemia may lead patients to become transfusion dependent (TD), potentially impacting overall survival (OS). This research aims at better understanding the impact of transfusion status (TS) on OS and other clinical, economic, and humanistic outcomes in patients with MDS. METHODS: We conducted 2 systematic literature reviews (SLRs) to understand the impact of TS on OS and its association with other clinical, economic, and humanistic outcomes in patients with MDS. Both SLRs compared: TD versus transfusion independent (TI) patients at baseline; patients who became TI versus those remaining TD after therapy; and TD patients with different transfusion burdens. RESULTS: The first SLR of 10 studies showed decreased OS in TD versus TI patients. These findings were confirmed by a meta-analysis reporting better OS for TI patients (hazard ratio [HR] 0.43, 95% credible interval [CrI] 0.33–0.55). In a sub-analysis assessing patients with lower-risk MDS, OS was longer in patients who became TI versus those who remained TD (HR 0.36, 95% CrI 0.21–0.55; 63.4% decreased risk of death among TI versus TD patients). The second SLR of 28 studies showed better prognosis for other outcomes, including AML- and leukemia-free survival in TI patients. The meta-analysis showed a trend towards higher risk of AML progression and cumulative non-leukemic death in TD patients. Lower healthcare resource utilization, better quality of life, and reduced non-leukemic death for TI patients were also observed. CONCLUSIONS: These findings contribute to better understanding of the association between TS, OS, and other clinical, economic, and humanistic outcomes in patients with MDS. Better clinical, economic, and humanistic outcomes for TI patients were observed, suggesting that TD patients have worse prognoses.