First, we want to find out whether computer-assisted surgery (CAS) for total knee arthroplasty (TKA), which does not require opening the femoral medullary canal, results in a lesser C-reactive protein (CRP) level increase postoperatively compared to manual TKA. Second, they seek to examine whether the CRP reduction in CAS TKA and manual TKA follows a similar pattern within the first 2 weeks after surgery. Third, the study aims to compare and analyze the CRP levels in 3 different groups: CRP levels in CAS TKA with surgeons who started TKA surgery by CAS, CRP levels in manual TKA by surgeons with little experience, and CRP levels in skillful manual TKA performed after conducting over 200 cases. The 3 patient groups were as follows. Group 1: Patients who underwent non expertized surgeon CAS TKA (N = 63). Group 2: Patients who underwent manual TKA after surgeon CAS TKA experience (N = 108). Group 3: Patients who underwent manual TKA after surgeon 200 cases or more of either CAS TKA or manual TKA experience (more skillful manual TKA) (N = 66). CRP levels were analyzed using electronic medical records for 3 time points: within 3 months before surgery, 5 days after surgery, and 11 days after surgery. There were no statistically significant differences in pre operative CRP values among the 3 groups. At 5 days after surgery, the CRP level were 48.59 ± 32.75 for CAS TKA, 69.82 ± 42.76 for early manual TKA, and 67.73 ± 44.00 for skillful manual TKA, indicating a statistically significant lower CRP level in the CAS TKA group compared to the manual TKA groups (P = .01). At 11 days after surgery, there were no statistically significant differences in CRP level among the 3 groups, with was 12.12 ± 9.74 for CAS TKA, 14.07 ± 13.18 for early manual TKA, and 11.43 ± 11.45 for skillful manual TKA. The degree of CRP elevation after TKA is related to bone and medullary injury rather than soft tissue.