Total knee arthroplasty (TKA) improves patients' Health-related quality of life (HRQoL) compared to before surgery. However, based on our knowledge, the improvement in HRQoL after TKA, which depends on various factors, has yet to be investigated compared to healthy people. This study aimed to evaluate the HRQoL of patients compared to healthy people and the factors affecting the HRQoL after TKA. In this matched case-control study (1002 participants), HRQoL in 501 patients who underwent TKA between 2015 and 2022 at Shafa Yahyainan Hospital affiliated with Iran University of Medical Sciences were compared with 501 healthy controls. HRQoL was evaluated in two parts (before compared to 12 months after TKA and 12 months after TKA compared to the healthy population). The 36-item short-form health survey (SF-36) was used to evaluate HRQoL 12 months after surgery. The influencing factors on HRQoL were evaluated by multivariate logistic regression analysis. No significant difference was observed in the demographic characteristics of the participants in the two groups. The mean overall SF-36 score, 12 months after surgery, significantly improved compared to before surgery (64.21 ± 22.2 vs. 37.55 ± 15.13, p:0.001). The mean total score of SF-36 was statistically similar between the case and control groups (64.21 ± 22.2 VS 72.53 ± 25.3). The multivariate analysis showed that sex, BMI, number of comorbidities, postoperative compliance, and complications were significantly related to the decrease in patients' HRQoL (P < 0.001).TKA can improve the HRQoL except for two subscales of happiness/vitality and physical performance, similar to the healthy population. Female gender, obesity and overweight, comorbidity, bilateral TKA, non-adherence to postoperative physiotherapy, and complications were associated with decreased HRQoL.