This study evaluated the effects of intramedullary instrumentation when used on the femur and tibia. Twenty-six patients (52 knees) undergoing bilateral index cemented total knee arthroplasty were analyzed. Bilateral knee arthroplasties were chosen because the increased surgery would theoretically maximize any perioperative hemodynamic or hematologic changes. Patients were randomized into one of two groups depending on the exact form of surgical instrumentation used. Group I (intramedullary) knees were implanted with standard intramedullary fluted instruments. No special measures to vent the entrance holes were made. Group II (extramedullary) knees were implanted with an extramedullary tibial guide, in conjunction with an intramedullary femoral guide placed through a vented femoral hole. All patients manifested significant changes in their hematologic and hemodynamic values after arthroplasty. Leukocytes increased 85% on average, whereas fibrinogen (106%) and erythrocyte sedimentation rates (145%) also showed significant increases. Conversely, patients exhibited a relative thrombocytopenia (63%) nadiring on the second postoperative day. However, there was no significant differences seen between the two instrumentation groups. Hemodynamically, all patients exhibited rises in cardiac index (52%) and pulmonary artery pressures (64%). Analysis of the hemodynamic results in this study does demonstrate subtle evidence of increased pulmonary vascular resistance in the intramedullary group. Specifically, the intramedullary group had lower cardiac indexes, in association with higher pulmonary pressures. This increase in pulmonary vascular resistance with the use of intramedullary instrumentation may represent subtle evidence of increased lung injury in this group. Results point to the continued use of fluted intramedullary rods and vented entrance holes as a reasonable surgical technique in patients undergoing knee arthroplasty.