We sought is to determine the mechanism of failure among primary total knee arthroplasties (TKAs) performed at a single high-volume institution by asking the following research questions: (1) What are the most common failure modes for modern TKA designs? and (2) What are the preoperative risk factors for failure following primary TKA? From May 2007 to December 2012, 18,065 primary TKAs performed on 16,083 patients at a single institution were recorded in a prospective total joint arthroplasty registry with a minimum of 5-year follow-up. We retrospectively reviewed patient charts to determine a cause of failure for primary TKAs. A cox proportional hazard model was used to determine the risk of revision surgery following primary TKA. The most common reasons for failure within 2 years after TKA were infection and stiffness. The multivariable regression identified the following preoperative risk factors for TKA failure: history of drug abuse (hazard ratio HR 4.68; P = 0.03), deformity/mechanical preoperative diagnosis (HR 3.52; P < .01), having a constrained condylar knee implant over posterior-stabilized implant (HR 1.99; P < .01), post-traumatic/trauma preoperative diagnosis (HR 1.78; P = .03), and younger age (HR 0.61; P < .01) These findings add to the growing data that primary TKAs are no longer failing from polyethylene wear-related issues. This study identified preoperative risk factors for failure of primary TKAs, which may be useful information for developing strategies to improve outcomes following TKA.