One hundred consecutive, primary simultaneous bilateral total knee arthroplasties were prospectively compared with 100 consecutive, primary unilateral total knee arthroplasties in reference to relative risk, complications, cost, and need for rehabilitation. All procedures were performed using identical preoperative, intraoperative, and postoperative protocols. Postoperative confusion was approximately four times greater in the simultaneous bilateral total knee arthroplasties group (29% versus 7%), which was thought to represent an increased incidence of fat embolism. Cardiopulmonary complications were approximately three times greater after simultaneous bilateral total knee arthroplasties (14% versus 5%), and most commonly involved arrhythmias. The increased stress on the cardiopulmonary system with simultaneous bilateral total knee arthroplasties may make this procedure contraindicated in certain patients with preexisting disease. There was an approximately 17 times greater need for banked blood in the simultaneous bilateral total knee arthroplasties group (17% versus 1%), which is alarming given the persistent concerns of transfusion related disease transmission. Although the length of hospitalization was similar (6.4 days simultaneous bilateral total knee arthroplasties versus 6 days unilateral total knee arthroplasty), 89% of the patients in the simultaneous bilateral total knee arthroplasties group required a rehabilitation stay versus 45% of the patients in the unilateral total knee arthroplasty group. Total hospital charges averaged $53,168 for simultaneous bilateral total knee arthroplasties versus $32,598 for unilateral total knee arthroplasty. Total rehabilitation charges were similar. The relative cost savings implicit by doing simultaneous bilateral total knee arthroplasties seem to be at least partially offset by the approximately two times greater need for rehabilitation in this group. The true safety, efficacy, relative risk, and total cost analysis of simultaneous bilateral total knee arthroplasties demands further critical evaluation.