Background: Refractoriness to platelet transfusion, prevalent among 15-20% of hemato-oncological patients, is associated with multitransfusions and inferior outcomes. We evaluated the effectiveness of extended slow-dose transfusion (ESDT) in increasing platelet increments in multitransfused patients. Methods: Patients treated after the implementation of ESDT were compared with historical controls treated with standard single-donor platelet (SDP) transfusions. Cohorts of early and late recipients were assembled for comparison, i.e. the 8th or 9th and 11th platelet unit per patient, respectively. Patients in the ESDT group received transfusions equal to half an SDP unit, administered over 4 h. Effectiveness was defined as a higher corrected count increment (CCI) at 1, 12, and 24 h after transfusion. Results: In the early-recipients cohort, 24-h-posttransfusion increments were available for 29 ESDT patients and 6 standard patients, and did not differ significantly between the groups (p = 0.078). The 24-h-posttransfusion increment was available for 20 ESDT patients and 7 standard patients in the late-recipients cohort. The CCI was significantly higher in the ESDT group (p = 0.042). ABO compatibility improved the CCI (p = 0.01). Conclusions: ESDT demonstrated slightly higher increments at 24 h after transfusion in late recipients, suggesting this could be a cost-effective approach for the treatment of thrombocytopenic multitransfused hemato-oncological patients.