Background: Total knee arthroplasty (TKA) is a procedure that has a risk of perioperative blood loss and allogeneic blood transfusion. The purpose of the present study was to compare the perioperative blood loss and transfusion rate between the 3-hour interval clamping and 12-hour interval clamping of closed suction drainage after simultaneous bilateral total knee arthroplasty (SBTKA). Methods: A total of 122 SBTKAs were enrolled in this retrospective study. A 3-hour clamping protocol was applied in 53 SBTKAs and a 12-hour clamping protocol was applied in 69 SBTKAs. The amount of perioperative blood loss, transfusion requirements, postoperative hemoglobin and hematocrit levels, the lowest hemoglobin and hematocrit levels during hospitalization, readmission within 90 days, and clinical outcomes were compared between the 3-hour clamping group and the 12-hour clamping group. Results: The 12-hour clamping group had fewer patients requiring transfusion (26.1%, 18/69) than did the 3-hour clamping protocol group (49.1%, 26/53) (p = 0.008). The 12-hour clamping group had a lower amount of estimated blood loss (1,426.9 ± 421.5 mL) than did the 3-hour clamping protocol group (1,882.1 ± 445.6 mL) (p < 0.001). The 12-hour clamping group showed higher hemoglobin and hematocrit levels (both p < 0.001) on postoperative day 5 than did the 3-hour clamping group. The lowest hemoglobin and hematocrit levels were higher in the 12-hour clamping group than in the 3-hour clamping group (p = 0.039 and p = 0.016, respectively). Within 1 postoperative month, there were 2 cases of wound dehiscence in each group (p = 0.585). But, at 1 year after the operation, no serious complications occurred in the two groups. Conclusions Compared to the 3-hour clamping protocol, the 12-hour clamping protocol significantly reduced transfusion requirements, estimated blood loss volume, and hemoglobin and hematocrit levels after SBTKA. We suggest that 12-hour temporary clamping should be considered for reducing transfusion rates.