The Zimmer iASSIST system is a novel accelerometer-based navigation system for TKA. 76 patients (76 knees) were prospectively matched for age, BMI, gender, diagnosis, and pre-operative scores, and underwent TKA using the iASSIST (n=38) or optical CAS (n=38). There were no significant differences in clinical outcomes or satisfaction rates at six months post-operatively (P>0.05). Mechanical axis was 1.8±1.3° in the iASSIST cohort versus 2.1±1.6° in the CAS cohort (P=0.543). There were no significant differences in number of outliers for mechanical axis (P=1.000), coronal femoral-component angle (P=0.693), coronal tibial-component angle (P=0.204) or joint line deviation (P=1.000). The duration of surgery was significantly longer in the CAS group (P<0.001), while the added cost of accelerometer-based navigation was approximately $1000 per operation.