Antibiotics, heparin, and several surgical interventions have been used in various combinations for the treatment of septic thrombophlebitis, but the optimal management remains unclear. There are limited data from comparative trials studying this issue. Specifically, only one randomized controlled trial was conducted, while the rest of the evidence comes from case series and case reports. The results of this systematic review of septic thrombophlebitis suggest that the use of heparin in combination with antibiotics is associated with low mortality in patients with this serious type of infection. In addition, adverse effects related to heparin were limited in the reported literature. Although data from comparative trials are required to draw definitive conclusions, the available evidence suggests that the administration of heparin should be considered early in the management of patients with septic thrombophlebitis.