Patients with knee osteoarthritis (OA) often present with symptoms that warrant bilateral TKAs. There are potential benefits to operating on both knees on the same day, but the safety of simultaneous bilateral TKAs has been questioned. To evaluate whether there were any differences in 30-day mortality between patients having simultaneous bilateral TKAs and those having staged bilateral TKAs, we analyzed data from the Swedish Knee Arthroplasty Register and the Swedish Cause of Death Register. We included 48,931 patients with OA having 60,062 primary TKAs during 1985 to 2004; 1139 had surgery on both knees on the same day (simultaneous bilateral) and 3432 had surgery on both knees on two different occasions with less than 1 year between operations (staged bilateral). The 30-day mortality after simultaneous bilateral TKAs was 7.53 (confidence interval, 2.62-21.69) times higher than after the second of staged TKA and 3.77 (confidence interval, 2.04-6.98) times higher than after a primary unilateral TKA. Assuming the total risk for a staged procedure is twice that of a unilateral procedure, the risk of mortality within 30 days is 1.94 (confidence interval, 1.05-3.59) times higher with simultaneous than staged TKA. It is safer to operate on one knee at a time. Level of Evidence: Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.