As the coronavirus disease 2019 (COVID-19) global pandemic continues, multiple vaccines have been developed to decrease infection rate and number of deaths. Vaccine administration is especially important as new COVID-19 variants emerge. While the number of severe thromboembolic events reported after adenovirus-based vaccination has gained attention, there is little information regarding the presentation and management of post-vaccination venous thromboembolism (VTE). Here, we present two cases of VTE after the Janssen vaccine administration. In the first case, a 98-year-old African American female with hypertension developed bilateral lower extremity edema that evolved into unilateral lower extremity edema 20-35 days following the Janssen vaccine administration. She was found to have an extensive unilateral proximal femoral deep vein thrombosis (DVT) 35 days after the vaccination. In the second case, a 64-year-old African American female developed ecchymosis and unilateral edema six days after the Janssen vaccine administration. She was found to have proximal superficial vein thrombosis two days later. In both cases, laboratory data, including platelets and anti-heparin antibodies were within normal limits. Thus, VTE may be an adverse effect of the Janssen vaccine or any adenovirus-based vaccine, but further surveillance and investigation to elucidate this association are necessary. We advise practitioners to have a high index of suspicion for thrombosis after Janssen vaccine administration, regardless of the presence of thrombocytopenia, and avoidance of heparin products until heparin antibody results return.