Objective: To explore the differences of alignment and operative time between portable accelerometer-based navigation device (PAD) and computer assisted surgery (CAS) in total knee arthroplasty (TKA). Methods: Data of patients using iASSIST (a kind of PAD) and OrthoPilot (a kind of CAS) for TKA in Peking University Third Hospital from December 2017 to December 2019 were retrospectively collected. The differences of preoperative general data, preoperative alignment, operative time and postoperative alignment were studied between the two groups. Results: A total of 82 patients were enrolled in our study, including 40 patients in the PAD group and 42 patients in the CAS group. Gender, age, body mass index (BMI), surgical side, preoperative hip-knee-ankle (HKA) angle and preoperative HKA angle deviation didn’t show statistically significant difference between the PAD group and the CAS group (P>0.05). Postoperative HKA angle (180.8°±2.2° vs.181.8±1.6°, t=-2.458, P=0.016) and postoperative coronal femoral-component angle (CFA, 90.6°±1.8° vs. 91.6°±1.6°, t =-2.749, P=0.007) of the PAD group were smaller than those of the CAS group, but there was no significant difference in coronal tibia-component angle (CTA, 90.0°±1.3° vs.89.6°±1.4°, t=1.335, P=0.186) between the two groups. There was no significant difference in the rate of outliers (varus or valgus>3°) for postoperative HKA angle (10.0% vs.11.9%,χ2 =0.076,P=0.783), CFA (12.5% vs. 14.3%, χ2=0.056, P=0.813) and CTA (2.5% vs. 0%, χ2=1.063, P=0.303). There was no significant difference in the accuracy of postoperative HKA angle (2.1° vs. 2.0°, t=0.055, P=0.956), CFA (1.4° vs. 1.8°, t=-1.365, P=0.176) and CTA (1.0° vs. 1.1°, t=-0.828, P=0.410) between the two groups. The precision of postoperative HKA angle (1.1° vs. 1.3°, F=1.251, P=0.267), CFA (1.3° vs. 1.4°, F=0.817, P=0.369) and CTA (0.8° vs. 0.9°, F=0.937, P=0.336) were also not significantly different. We also didn’t find statistically significant difference in operative time between the two groups [(83.4±25.6) min vs. (86.5±17.7) min, t=-0.641,P=0.524]. Conclusion: PAD and CAS had similar accuracy and precision in alignment in TKA, and there was no significant difference in operative time, which indicates that PAD has a broad application prospect in TKA.