173 obese patients scheduled for total knee arthroplasty were randomized to have the procedure performed with either patient-specific instrumentation (PSI) or conventional instrumentation (CONV). The primary purpose of this study was to evaluate cost-effectiveness of PSI relative to CONV after 12 weeks, using the Western Ontario and McMaster Universities Osteoarthritis Index as the measure of efficacy. Results from the public health payer perspective suggested high cost and reduced effectiveness with PSI compared to CONV. Results from the societal perspective suggested lower cost and reduced effectiveness with PSI compared to CONV.