Background: To analyze evolution and factors related with greater gains in Health Related Quality of Life (HRQOL) and with a greater probability of exceed their corresponding minimal clinically important differences (MCID) in patients with Osteoarthritis of the knee, undergoing total knee arthroplasty (TKA) at long-term.Methods: Data were obtained from two previously recruited multicenter cohorts of patients who underwent TKA in the Basque Country. Patients were follow-up at 6 months and 10 years after surgery. Patients completed specific and generic HRQOL questionnaires plus sociodemographic, and clinical data at 10 years. Associations were analysed using linear and logistic regression models.Results: A total of 471 patients responded at 10-year follow-up. The multivariable analysis showed that low preoperative HRQOL scores, higher age, higher BMI, some comorbidities and readmissions at 6 months were associated with less gains in HRQOL. Apart from aforementioned, to have a peripheral vascular disease (odd ratio 0.49 (95% CI, 0.24–0.99)), complications (odd ratio 0.31 (95% CI, 0.11–0.91)), and readmissions within 6 months of discharge (odd ratio 2.12 (95% CI, 1.18–3.80)) were associated with a lower probability of exceeding the MCID. The effect sizes (ESs) of changes from baseline to 6 months (range, 1.20–1.96) and to 10 years (range, 1.54–1.99) were large in all dimensions, nevertheless the ESs from 6 months to 10 years were not appreciable for pain (ES = 0.03) or stiffness (ES = 0.09), and small for function (ES = 0.30).Conclusions: Low preoperative HRQOL scores, to be elderly, severe obesity, the presence of some comorbidities -depression and rheumatology disease-, having readmissions or complications and not having rehabilitation of discharge, are good predictors of long-term lower gains in HRQOL. Some other non-registered parameters of the follow-up may also influence those outcomes.Key Indexing Terms (MeSH terms): Health-Related Quality of Life, Knee Arthroplasty, Total, Osteoarthritis