Background: Leukoreduction of blood products is commonly performed in human medicine, but its effect on outcome or incidence of transfusion reactions (TRs) in dogs is unknown.Objectives: To prospectively evaluate the incidence of acute TRs in, and the outcome of, dogs receiving either leukoreduced (LR) or nonleukoreduced (N-LR) packed red blood cells (PRBC).Animals: Dogs (n = 194) administered PRBC between August 2017 and June 2020.Methods: Prospective randomized double-blinded clinical trial. Dogs were randomized to receive either LR or N-LR PRBC and clinicians, nurses and investigators were blinded to the group allocations. The incidence of TRs, change in PCV, hospitalization duration, and survival to discharge were recorded.Results: Out of the 194 dogs, 96 received LR and 98 received N-LR PRBCs. The mean 12-hour change in PCV value was +9.22% (SD 5.27%) for dogs that received N-LR and +10.69% (SD 6.44%) for dogs that received LR PRBC (effect size 0.26, 95% confidence interval [CI] À0.02 to 0.55), which was not significantly different (P = .08). TRs were documented in 16/194 (8.24%) dogs, with 1/194 (0.51%) being a mild allergic reaction, while 15/194 (7.73%) had suspected febrile nonhemolytic TRs (FNHTRs). FNHTR incidence was not significantly different between the LR (6/96, 6.25%, 95% CI 2.8-13.56) and N-LR (9/98, 9.18%, 95% CI 4.92-17.11) groups