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Background Study Design and Methods Results Discussion Volume‐reduced platelets can minimize circulatory overload, allergic transfusion reactions, or out‐of‐group plasma infusion. Our center adopted a volume reduction protocol that includes acidification with acid citrate dextrose solution A (ACD‐A) before centrifugation and without any rest period prior to resuspension allowing a better turnaround time for platelet issue.This report compares corrected count increments (CCIs) from full‐volume and ACD‐A acidified volume‐reduced human platelets in a retrospective study at a single hospital and in a mouse model.At a pediatric tertiary care hospital, 530 patients received conventional apheresis platelets during the 20‐month study period. Among all patients, the expected 4‐h mean CCI was 9.8 (95% CI: 8.7, 10.9) for full‐volume platelets, and 8.8 (95% CI: 7.3, 10.6) for ACD‐acidified volume‐reduced platelets (p = .29). A statistically significant difference (p = .01) was identified in the expected 24‐h mean CCI: 6.3 (95% CI: 5.5–7.0) with full‐volume platelet, 4.7 (95% CI: 3.6–6.0) with ACD‐acidified volume‐reduced platelet. Limiting CCI calculations to patients with Hematology/Oncology/Hematopoietic Progenitor Cell Transplant diagnosis (n = 296, 56%) indicated a statistically significant difference in both 4‐ and 24‐h predicted CCIs, showing lower CCIs in ACD‐acidified volume‐reduced platelet, although these were still similar to the CCIs observed in all patients and considered to be clinically acceptable responses similar to other volume reduction protocols. The recovery of count‐adjusted, volume‐reduced platelets was significantly lower in mice, suggesting a procedure‐related defect.ACD‐A acidification of platelets before volume reduction decreases turnaround time for platelet issue and provides clinically allowable 4‐h and 24‐h platelet increments. [ABSTRACT FROM AUTHOR]