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Purpose: Decades of innovations in total knee arthroplasty (TKA) design have led to large number of possible prosthesis combinations in regards fixation, posterior stability, bearing mobility, bearing surface, and patella resurfacing, each of which can alter the revision risk. The accumulative effect when the lowest risk combination in each design category, or "Optimum Prosthesis Combination" (OPC) is utilized remains unknown. The purpose of this analysis was to first, identify the OPC and second, to compare the revision risk of a cohort who received the OPC to a cohort who received an Alternative Prosthesis Combination (APC).Methods: National registry revision risk data for primary TKA for osteoarthritis were obtained from September 1999 to December 2015 for two patient cohorts, those receiving an OPC and those receiving an APC. OPC was defined as TKA with the lowest revision risk option for five primary TKA design categories; fixation, posterior stability, bearing mobility, bearing surface, and patella resurfacing, while APC had one or more higher risk options.Results: Of the 482,373 included TKA, 42,008 (8.7%) were in the OPC cohort, who received a minimally stabilized, fixed bearing TKA with cross-linked polyethylene with patella resurfacing. Both cohorts had similar demographics. At 10 years, the OPC cohort had a Cumulative Percent Revision of 2.4% (95% CI 2.1, 2.8) compared to 5.5% (95% CI 5.4, 5.6) for the APC cohort. For all patients, revision risk of the APC cohort was higher at all times [151% greater at ≥ 3 years (p < 0.001)]. Loosening/lysis was the most common cause of revision in the ACP cohort (1.1%), while it was the second most common cause in the OPC cohort (0.3%). The increased risk was apparent in all age and gender subgroups, with the highest risk increase seen in males ≥ 65 years.Conclusions: Patients receiving the lowest risk prosthesis design combination or Optimum Prosthesis Combination TKA had a 60% lower revision risk, with similar demographics to the Alternative Prosthesis Combination TKA.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]