Background: The Mirasol® Pathogen Reduction Technology System was developed to reduce transfusion‐transmitted diseases in platelet (PLT) products. Study Design and Methods: MiPLATE trial was a prospective, multicenter, controlled, randomized, non‐inferiority (NI) study of the clinical effectiveness of conventional versus Mirasol‐treated Apheresis PLTs in participants with hypoproliferative thrombocytopenia. The novel primary endpoint was days of ≥Grade 2 bleeding with an NI margin of 1.6. Results: After 330 participants were randomized, a planned interim analysis of 297 participants (145 MIRASOL, 152 CONTROL) receiving ≥1 study transfusion found a 2.79‐relative rate (RR) in the MIRASOL compared to the CONTROL in number of days with ≥Grade 2 bleeding (95% confidence interval [CI] 1.67–4.67). The proportion of subjects with ≥Grade 2 bleeding was 40.0% (n = 58) in MIRASOL and 30.3% (n = 46) in CONTROL (RR = 1.32, 95% CI 0.97–1.81, p =.08). Corrected count increments were lower (p <.01) and the number of PLT transfusion episodes per participant was higher (RR = 1.22, 95% CI 1.05–1.41) in MIRASOL. There was no difference in the days of PLT support (hazard ratio = 0.86, 95% CI 0.68–1.08) or total number of red blood cell transfusions (RR = 1.12, 95% CI 0.91–1.37) between MIRASOL versus CONTROL. Transfusion emergent adverse events were reported in 119 MIRASOL participants (84.4%) compared to 133 (82.6%) participants in CONTROL (p = NS). Discussion: This study did not support that MIRASOL was non‐inferior compared to conventional platelets using the novel endpoint number of days with ≥Grade 2 bleeding in MIRASOL when compared to CONTROL. [ABSTRACT FROM AUTHOR]