Background and objectives: Deep vein thrombosis (DVT) is one of the most serious post-operative complications in the case of total knee arthroplasty (TKA). This study aims to verify the predictive role of inflammatory biomarkers [monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI)] in acute DVT following TKA. Materials and methods: The present study was designed as an observational, analytical, retrospective cohort study and included all patients over 18 years of age with surgical indications for TKA, admitted to the Department of Orthopedics, Regina Maria Health Network, Targu Mures, Romania, and the Department of Orthopedics, Humanitas MedLife Hospital, Cluj-Napoca, Romania between January 2017 and July 2022. The primary endpoint was the risk of acute DVT following the TKA, and the secondary endpoint was the length of hospital stay, and the outcomes were stratified for the baseline’s optimal MLR, NLR, PLR, SII, SIRI, and AISI cut-off value. Results: DVT patients were associated with higher age (p = 0.01), higher incidence of cardiac disease [arterial hypertension (p = 0.02), atrial fibrillation (p = 0.01)], malignancy (p = 0.005), as well as risk factors [smoking (p = 0.03) and obesity (p = 0.02)]. Multivariate analysis showed a high baseline value for all hematological ratios: MLR (OR: 11.06; p < 0.001), NLR (OR: 10.15; p < 0.001), PLR (OR: 12.31; p < 0.001), SII (OR: 18.87; p < 0.001), SIRI (OR: 10.86; p < 0.001), and AISI (OR: 14.05; p < 0.001) was an independent predictor of DVT after TKA for all recruited patients. Moreover, age above 70 (OR: 2.96; p = 0.007), AH (OR: 2.93; p = 0.02), AF (OR: 2.71; p = 0.01), malignancy (OR: 3.98; p = 0.002), obesity (OR: 2.34; p = 0.04), and tobacco (OR: 2.30; p = 0.04) were all independent predictors of DVT risk. Conclusions: Higher pre-operative hematological ratios MLR, NLR, PLR, SII, SIRI, and AISI values determined before operations strongly predict acute DVT following TKA. Moreover, age over 70, malignancy, cardiovascular disease, and risk factors such as obesity and tobacco were predictive risk factors for acute DVT.