Objective To compare the clinical efficacy of cruciate retaining and posterior stablized prosthesis during initial and unilateral knee arthroplasty, as well as their influences on limb swelling and limb function recovery. Methods A total of 160 knee osteoarthritis patients who underwent total knee arthroplasty from December 2016 to December 2018 were selected and assigned to cruciate retaining group and posterior stablized group according to knee joint prosthesis types, with 80 cases in each group. Patients adopted initial and unilateral knee arthroplasty with cruciate retaining and posterior stablized prosthesis, respectively. Their postoperative serum inflammatory response, limb function recovery, and clinical efficacy were assessed. Results After respective treatments, the serum C-reactive protein and IL-6 levels of the two groups were lower than before (P<0.05). The knee joint function scores of the two groups after respective treatments were higher than before (P<0.05). The knee joint function scores of the cruciate retaining group 3 and 6 months after discharge were higher than those of the posterior stablized group (P<0.05). Conclusion During initial and unilateral knee arthroplasty, the cruciate retaining prosthesis can improve limb function and reduce serum inflammatory response.