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In total knee arthroplasty (TKA), reconstruction of a neutral mechanical axis is of great importance. The main goal of this study was to compare the accuracy of alignment after conventional versus computer-assisted TKA. Additionally, the effect of computer-assisted surgery (CAS) on functional outcome was analyzed. Out of a consecutive series, 50 conventional TKA were compared with 50 computer-assisted TKA. Except for the use of CAS, all perioperative and postoperative interventions were comparable. Radiological outcome was analyzed on standardized standing long-leg radiographs. Functional outcome was assessed using the Oxford Knee Score (OKS) and the Knee Society Score (KSS). No significant difference in mean mechanical axis alignment between the two groups was found. The number of outliers deviating more than 3 degrees from the mechanical axis was significantly reduced by using CAS, with 50% outliers in the conventional group and 26% outliers in the CAS group (p = 0.023). At midterm follow-up, the OKS and KSS knee and function scores did not show statistical difference between the two groups. The present study showed a reduction of the number of outliers exceeding 3 degrees from the tibiofemoral mechanical axis using CAS-TKA. This improvement in accuracy did not result in improvement of the functional outcome at mid-term follow-up.