We wished to determine whether simultaneous bilateral sequential total knee replacement (TKR) carried increased rates of mortality and complications compared with unilateral TKR in low- and high-risk patients. Our study included 2385 patients who had undergone bilateral sequential TKR under one anaesthetic and 719 who had unilateral TKR. There were no significant pre-operative differences between the groups in terms of age, gender, height, weight, body mass index, diagnosis, comorbidity and duration of follow-up, which was a mean of 10.2 years (5 to 14) in the bilateral and 10.4 years (5 to 14) in the unilateral group. The peri-operative mortality rate (eight patients, 0.3%) of patients who had bilateral sequential TKR was similar to that (five patients, 0.7%) of those undergoing unilateral TKR. In bilateral cases the peri-operative mortality rate (three patients, 0.4%) of patients at high risk was similar to that (five patients, 0.3%) of patients at low risk as it was also in unilateral cases (two patients, 1.0% vs three patients, 0.6%). There was no significant difference (p = 0.735) in either the overall number of major complications between bilateral and unilateral cases or between low- (p = 0.57) and high-risk (p = 0.61) patients. Also, the overall number of minor complications was not significantly different between the bilateral and unilateral group (p = 0.143). Simultaneous bilateral sequential TKR can be offered to patients at low and high risk and has an expected rate of complications similar to that of unilateral TKR.