Aim: Total knee replacement (TKR) is a common procedure worldwide that is considered cost-effective with excellent long-term survivorship. This study aimed to assess health-related quality of life (HQOL), functional status, and associated factors before and after 3 to 12 months of TKR. Furthermore, several demographical factors were included in this study to evaluate the potential association with the procedure’s outcome. Methods: This study was a cross-sectional study including 118 selected patients from January 2020 to January 2021. Western Ontario and McMaster Universities Osteoarthritis Index scale (WOMAC) and Short Form-36 (SF-36) scale were used in this study. Results: Patients before the TKR operation experienced severe pain, joint stiffness, physical impairment, and psychological demand issues. After the TKR operation, all symptoms were improved significantly. It was found that the main change occurred 6-12 months after the procedure. Gender and age were found to be the primary predictor of quality of life among TKR patients. Conclusion: TKR procedure can provide an overall improvement in the quality of life for patients. The improvement can be detected for several months after the procedure. Function and pain are the most critical indicators of improvement in quality of life. Assessing the quality of life is a key indicator for identifying patients without improvement, and essential for improving the health care process and comparing other alternatives to an intervention.