BACKGROUND: Platelet (PLT) support is critical to the care of patients with thrombocytopenia, but allogeneic transfusions carry risk. Pathogen reduction mitigates some transfusion risks, but effects on PLT function remain a concern. This clinical pilot study assessed the effect of pathogen reduction technology with riboflavin plus ultraviolet light using thrombelastography (TEG). STUDY DESIGN AND METHODS: This prospective, randomized, crossover study compared Mirasol-treated (MIR) and standard reference (REF) PLT transfusions. PLT counts and TEG measurements were taken at pretransfusion and 1- and 24-hour-posttransfusion time points. The primary outcome measure was the pretransfusion to 1-hour-posttransfusion change in maximum amplitude (ΔMA1hr). Secondary endpoints included ΔMA among other time points, relative MA, and the PLT count–MA correlation. RESULTS: Of 16 enrolled patients, one withdrew before study treatment and three did not require two transfusions, leaving 12 patients in the efficacy analyses (seven MIR-REF, five REF-MIR). ΔMA1hr (mean ± SD) was 10.60 ± 6.47 mm for MIR and 14.33 ± 5.38 mm for REF (p = 0.20, n = 10). ΔMA24hr was 9.49 ± 7.94 for MIR and 7.13 ± 3.08 for REF (p = 0.38, n = 9); ΔMA24hr-1hr was −1.11 ± 2.95 for MIR and −7.20 ± 4.81 for REF (p = 0.016, n = 8). MA values for MIR and REF correlated with the log of PLT count (rMIR = 0.6901, rREF = 0.7399). CONCLUSION: TEG is sensitive to changes in hemostatic function resulting from a single PLT transfusion. MIR and REF provided similar increments in hemostatic function in the immediate posttransfusion period and at 24 hours. A significant difference detected for ΔMA24hr-1hr suggests different PLT clearance mechanisms. The relationship of these variables to clinically meaningful outcomes, for example, bleeding events or transfusion requirements, has yet to be determined.