Caprini score and D-dimer are well-recognized markers in deep vein thrombosis (DVT) assessment. However, their utility in guiding post-arthroplasty DVT risk is hampered by susceptibility to various post-operative factors, limiting their effectiveness as reminders. Conversely, these markers exhibit greater stability in the pre-operative setting. Despite this, research on the pre-operative predictive value of Caprini score and D-dimer for DVT following primary total knee arthroplasty (TKA) remains scarce. In a retrospective study, we analyzed data from patients who underwent primary TKA, between August 2015 and December 2022. Upon admission, Caprini scores were assessed, and comprehensive blood panels were obtained from fasting blood samples. For all patients, lower limb vascular Doppler ultrasonography was performed pre-operatively to exclude those with pre-existing DVT, and all patients underwent DVT examination again post-operatively. Our study included 2,873 patients, averaging 67.98 ± 7.54years, including 676 men and 2,197 women. In this study, 303 (10.55%) patients developed postoperative DVT, and 57 (1.98%) cases presented with lower limb symptoms. DVT incidence in patients with pre-operative Caprini scores of 1-2 (6.50%), 3 (10.28%), and ≥ 4 (18.05%) showed significant differences (P < 0.05). DVT rates were 14.80% in patients with pre-operative D-dimer levels of ≥ 1mg/L, higher than the 8.98% in those with levels of < 0.5mg/L, and 10.61% in those with levels 0.5-1mg/L (P < 0.05). In patients with Caprini scores of 1-2 and D-dimer levels ≤ 0.5mg/L, the occurrence rate of postoperative DVT was only 5.84%. For patients with Caprini scores ≥ 4 and D-dimer levels ≥ 1.0mg/L, the postoperative DVT occurrence rate soared to 24.81%, with the OR(odds ratio) was 4.744 compared to the former group. Patients with preoperative higher Caprini scores and D-dimer are more likely to develop DVT after TKA. Additionally, those with a preoperative Caprini score ≥ 4 and D-dimer level ≥ 1.0mg/L have a significantly increased risk (24.81%) of developing DVT, identifying them as a high-risk group for DVT following TKA. These findings hold significant value for DVT risk stratification in primary TKA patients and the formulation of preoperative interventions to mitigate the risk of DVT.