Our goal was to determine by direct measurement of drain output whether intraoperative injection of bupivacaine with epinephrine significantly reduces postoperative blood loss in total knee arthroplasty (TKA). The study and control groups were primary TKAs performed by 1 surgeon using a single-cemented TKA design and a consistent postoperative protocol. The study group comprised 37 sequential TKAs injected intraoperatively with bupivacaine and epinephrine (one-third pericapsular, two-thirds peri-incisional). The control group included 71 sequential TKAs. The study group had 32% (95% confidence interval, 11%-48%), or 195 mL, less drain output (P = .006). There were no statistically significant differences in the transfusion rate or bleeding indices. Control and study groups were comparable regarding tourniquet times, intraoperative soft-tissue releases, preoperative anticoagulant use, and overall postoperative complications. Our study demonstrated a statistically significant decrease in TKA postoperative drain output with intraoperative injection of bupivacaine with epinephrine.