Background: Cancer is known to increase the risk of VTE when compared to the non-cancer population. Additionally, SARS-CoV-2 infection has been associated with hypercoagulability and VTE. A study by Patell et al noted similar cumulative incidence of thrombotic events (arterial and venous) in patients hospitalized with COVID-19 with active cancer than those without cancer (14.2% vs 18.2%). Data from the COVID-19 and Cancer Consortium (CCC19) Registry reported incidence of VTE of 7.6% in cancer patients within 90 days of hospitalization for COVID-19. However, it is unknown whether patients with cancer are at significantly higher risk for VTE in the setting of COVID-19 compared to cancer patients without COVID-19. Our study objectives were to: 1) determine the overall incidence of VTE in patients with cancer with and without COVID-19, regardless of hospitalization status; 2) assess the relative risk of VTE due to COVID-19 in cancer patients; 3) examine risk for VTE in cancer patients with COVID-19 based on certain demographic characteristics and comorbidities. Methods: An institutional retrospective cohort analysis was performed from March 1, 2020 through July 31, 2021. 228 patients with COVID-19 and cancer were identified and compared to matched controls without COVID-19 (n = 448) during the same study period based on age, gender, and BMI. Results: Incidence of VTE in cancer patients with COVID-19 was significantly higher than in cancer patients without COVID-19 (11% vs 3.1%) [RR 3.45, 95% CI 1.85-6.67]. There was no significantly increased risk of VTE in cancer patients with COVID-19 based on the following characteristics: non-White race, male gender, diabetes mellitus, hypertension, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and end-stage renal disease receiving dialysis. However, patients with any history of smoking (including current smokers) had increased risk of VTE compared to never-smokers (RR 2.2756, 95% CI 1.0498-4.9326). Conclusions: COVID-19 further increases the risk of VTE in cancer patients, a population with an independent risk factor for VTE at baseline. Whether the increased risk is additive or synergistic is currently unknown. Demographic factors and comorbidities that have been associated with increased severity of COVID-19 in other studies do not appear to significantly increase risk of VTE in cancer patients with COVID-19, with the exception of smoking status (either current or past). Given the impact on morbidity and mortality, further analyses, including with larger datasets, are warranted.