Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there have been nearly seven million deaths associated with COVID-19 and over thirteen billion total vaccine doses administered worldwide. This study aimed to evaluate the patient demographics and laboratory values that might help predict individuals at risk of having a DVT formation while hospitalized with COVID-19, focusing on the four major strains alongside the associated vaccination availability periods in the United States to devise risk stratification and management algorithms. This retrospective cohort study analyzed 4,429 COVID-19 positive patients admitted to a single, tertiary care institution from March 2020 - February 2024 who underwent venous duplex ultrasound due to clinical suspicion. Results: It was found that active chemotherapy treatment, higher weight (77.0 vs. 84.0 kg), and longer LOS to first duplex (5 vs. 10 days) were independent predictors of mortality. Additionally, men, older age (68 vs. 70 years old), medical history of DVTs, and longer LOS to first duplex (5 vs. 8 days) were prognostic for DVT formation. More importantly, the prevalence of DVT was not statistically different between each COVID-19 wave, despite diminished mortality and morbidity overtime. These factors should raise clinical suspicion for DVT formation and mortality among physicians. This study also demonstrated many non-predictive variables including COVID-19 as the principal diagnosis, BMI, smoking status, history of atrial fibrillation, stroke, CAD, vaccination status, and all laboratory values. This study helps establish a critical foundation to analyze trends of anticoagulant and systemic corticosteroid use in this COVID-19 patient population.