The Oxford Knee Score (OKS) is a patient-reported outcome questionnaire typically used to assess function and pain in patients undergoing total knee replacement (TKR). However, research is inconclusive as to which preoperative factors are important in explaining variation in outcome following TKR. The operative records of 12,709 patients who underwent primary TKR over a 9-year period were analyzed. The following variables were collected for each patient: age, sex, body mass index (BMI), Index of Multiple Deprivation decile rank, side of operation, diagnosis, the American Society of Anaesthesiologists (ASA) grade, preoperative OKS, EQ-5D index score, EuroQol visual analog scale (EQ-VAS) score, the postoperative OKS at 1 and 2 years. Generalized linear regression models were performed at 1 and 2 years to investigate the effect of the preoperative variables on the postoperative OKS. The effect of age, sex, BMI, Index of Multiple Deprivation decile rank, diagnosis, ASA grade, preoperative OKS, EuroQoL five-dimensional (EQ-5D) index score, and EQ-VAS score were all statistically significant in explaining the variation in OKS at 1 and 2 years postoperatively, with critical level of significance of 0.05 (5%). Being male aged 60 to 69 years of normal BMI, ASA grade I (fit and healthy), living in an affluent area, not reporting preoperative anxiety/depression, were associated with an enhanced mean postoperative OKS at both 1 and 2 years. When adjusted for potential confounding, age of 60–69 years, male sex, normal BMI, lower ASA grade, higher Index of Multiple Deprivation and higher pre-operative EQ-5D, EQ-VAS and OKS were identified as factors that resulted in higher post-operative OKS after primary TKR.