Objective To explore the differences of therapeutic effects between computer assisted surgery (CAS) and portable accelerometer-based navigation device (PAD) in total knee arthroplasty (TKA) by comparing the blood loss volume, operation time and postoperative lower limb alignment. Methods A total of 30 patients undergoing TKA with CAS or PAD in our hospital from November 2019 to August 2021 were retrospectively studied, of which there are 12 patients (with 12 knees of TKA) in CAS group and 18 patients (with 20 knees of TKA) in PAD group. The comparison of operation time, blood loss volume at 3 days after surgery and postoperative lower limb alignment were performed between two groups. Results There were no statistically significant differences in age, gender, body mass index (BMI), disease duration , surgical side, varus(or valgus) and Kellgren-Lawrance grading between 2 groups(P>0.05). The operation time of two groups were 106.67±11.42 mins and 115.10±24.19 mins and the blood loss volume at 3 days after surgery were 400.60±163.02 ml and 417.98±176.09 ml, separately, without statistically significant differences(P>0.05). There were no statistically significant differences in the postoperative HKA angle, HKA angle deviation, mMPTA, mLDFA and sFCA (P>0.05). VAS and HSS score of 2 groups after surgery were significantly improved compared with that before surgery, and the difference was statistically significant (P<0.05). Comparison of postoperative VAS score and HSS score between the two groups showed no statistical significance(P>0.05). Conclusion CAS and PAD has no significant difference in perioperative conditions, lower limb alignment and clinical effect. They can be selected flexibly according to their advantages and disadvantages in clinical practice.