This study aims to evaluate the 2-year post-operative clinical outcomes of patients undergoing total knee arthroplasty (TKA) with computer-assisted surgery (CAS) using the pinless BrainLAB (R) VectorVision (R) Knee 2.5 Navigation System versus standard CAS. A retrospective case-control study of 200 patients who underwent TKA with CAS from 2008 to 2012 was conducted. Patients in the pinless arm underwent a shorter duration of surgery compared to the standard CAS arm with 72 +/- 13 min and 83 +/- 11 min, respectively (p < 0.001), with improvement in Oxford Knee Score from 34 +/- 8 to 18 +/- 5 and 34 +/- 9 to 18 +/- 5, respectively, without statistically significant differences in clinical outcomes at 2 years.