Severe side effects of adenoviral-vectored-DNA COVID-19 vaccines such as thrombosis have been reported. Herein, we report a case of sudden massive deep vein thrombosis (DVT) in a young man with inferior vena cava anomaly 20 hours after the second dose of the mRNA vaccine for COVID-19. There was recurrence of iliofemoral DVT after one year, despite complete resolution and administration of prophylactic anticoagulants. We suggest that the sudden episode was triggered by the vaccine rather than the venous anomaly, which can be associated with recurrence due to inadequate venous return through the small and tortuous infrarenal veins or increased venous pressure and stasis. There are no standard guidelines for the management of DVT following mRNA vaccination. However, we highlight the importance of initial workups, regular follow-ups, and standard treatment options, including the continuous administration of prophylactic anticoagulants which should be considered to prevent recurrence.