BACKGROUND: Despite the growing interest in alternative alignment strategies, advancement in surgical technique, and implant design, several studies have demonstrated that a large number of patients continue to be dissatisfied following total knee arthroplasty (TKA). The purpose of this study was to outline differences in three-dimensional (3D) knee morphology associated with sex and deformity of the arthritic knee and compare these to available off-the-shelf and patient-specific implants. METHODS: A total of 85,604 preoperative computed tomography scans of patients undergoing TKA were analyzed. Distal femur geometry was quantified via 11 measurements taken from 3D models and landmarks. These values were then compared to the geometries of 12 common TKA implants from the American Joint Replacement Registry. RESULTS: The average overall alignment of the studied population was found to be 3.3° varus with the average hip-knee-ankle (HKA) angle being smaller in men than women. Femoral distal offset was found to play an important role in driving both varus and valgus deformities. Nearly 40% of knees in the cohort had a distal condylar offset (DCO) and 25.6% had a posterior condylar offset (PCO) that would require beyond the traditionally acceptable 3° varus/valgus or require internal rotation when using the most common off-the-shelf (OTS) implants on the market. The range of adequate coverage across the evaluated implant systems ranged from 20 to 63%. On average, less than half (41%) of the patient population fell within the bounds considered to be a proper fit for the 12 OTS implant systems evaluated. CONCLUSIONS: To our knowledge, this study is the largest 3D analysis of osteoarthritic knees to date and identified crucial differences in knee morphology among patients undergoing TKA. These data demonstrate a consistent asymmetry of femoral geometry, despite most off-the-shelf femoral implants being symmetric. In addition, there was a larger PCO and smaller DCO, questioning the utility of a single-radius femoral design in all patients.