Plasma transfusion is indicated for replenishment of coagulative proteins to stop or prevent bleeding. In 2014, the Netherlands switched from using ~300mL fresh frozen plasma units to 200mL solvent/detergent plasma units. We evaluated the effect of the introduction of solvent/detergent plasma on clinical plasma use, associated bleeding, and transfusion reaction incidences. Using diagnostic data from six Dutch hospitals, national blood bank data, and national hemovigilance data for 2011-2017, we compared the plasma/RBC units ratio (f) and the mean number of plasma and RBC units transfused for fresh frozen plasma (~300mL) and solvent/detergent plasma (200mL) for various patient groups, and calculated odds ratios comparing their associated transfusion reaction risks. Analyzing 13,910 transfusion episodes, the difference (Δf = fSD - fFFP) in mean plasma/RBC ratio (f) was negligible (Δfentire_cohort = 0.01 [95% confidence interval (CI) -0.02 to 0.05]; p=0.48). Solvent/detergent plasma was associated with fewer RBC units transfused per episode in gynecological (difference of mean number of units -1.66 [95% CI: -2.72, -0.61]) and aneurysm (-0.97 [-1.59, -0.35]) patients. Solvent/detergent plasma was associated with fewer anaphylactic reactions than fresh frozen plasma (odds ratio 0.37 [0.18, 0.77; p<0.01]) while the differences for most transfusion reactions were not statistically significant. Solvent/detergent plasma units, despite being 1/3 smaller by volume than fresh frozen plasma units, are not associated with a higher plasma/RBC ratio. Solvent/detergent plasma is associated with fewer anaphylactic reactions than fresh frozen plasma.