Objective To compare the effectiveness of the intermittent suture and the cosmetic suture in total knee arthroplasty (TKA). Methods A clinical data of 48 patients with knee osteoarthritis, who underwent initial TKA between January 2017 and April 2018, was retrospectively analyzed. Among them, 23 patients underwent intermittent suture (group A) and 25 patients underwent cosmetic suture (group B). There was no significant difference in gender, age, body mass index, disease duration, degrees of varus and valgus deformities, knee society score (KSS), visual analogue scale (VAS) score, and levels of interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) in serum before operation between the two groups (P>0.05). KSS scores at 1 and 6 months after operation were used to assess the knee function. VAS scores at 1, 3, and 5 days after operation were used to assess the pain degree of knee. Levels of IL-6, PCT, CRP, and ESR in serum at 1 day and 1 month after operation were recorded to evaluate the risk of periprosthetic infection. Likert score at 6 months after operation was used to evaluate the satisfaction of incision. The hospitalization time after operation was also recorded. Results All patients were followed up 7- 17 months (mean, 11.3 months). There was no significant difference in hospitalization time after operation between two groups (t=−1.907, P=0.063). The Likert score in group A was significantly lower than that in group B (t=−2.196, P=0.033). The VAS score, KSS clinical score and KSS functional score at different time points after operation were significantly better than those before operation in two groups (P<0.05). The VAS score at 5 days after operation was better than that at 1 day after operation in two groups, and the KSS clinical score and KSS functional score at 6 months after operation were better than those at 1 month after operation in two groups, all showing significant differences (P<0.05). The VAS scores at 3 and 5 days after operation were significantly lower in group B than in group A (P<0.05), and there was no significant difference in VAS score and KSS scores between two groups at other time points after operation (P>0.05). There was no significant difference in the levels of IL-6, PCT, CRP, and ESR between the two groups at different time points after operation (P>0.05). Conclusion Cosmetic suture is superior to intermittent suture in incision appearance and pain management, but there is no significant difference in short-term joint function and risk of periprosthetic infection after TKA.