About one third of patients who require one knee replacement have significant bilateral symptoms and will require surgery on both knees before achieving their full functional potential. The options for these patients are either to have one-stage bilateral knee replacements or two-stage knee replacements. Our aim was to compare the relative local and systematic morbidity of patients who had one-stage bilateral knee arthroplasty with those of patients who had unilateral total knee arthroplasty in a retrospective, consecutive cohort of patients to evaluate the safety of one-stage bilateral total knee arthroplasty. Seventy-two patients treated with one-stage bilateral knee replacements were matched for age, gender and year of surgery with 144 patients who underwent unilateral knee arthroplasty. We found one-stage bilateral arthroplasty was associated with significantly increased risks of wound infection, deep infection, cardiac complications and respiratory complications compared to unilateral knee arthroplasty. No increased risk of thromboembolic complications or mortality was found. We conclude that one-stage bilateral total knee arthroplasty is associated with increased risk of both systematic and local complications compared with unilateral knee replacement and therefore should be performed on only selective cases.