Background: Intramedullary nailing (IM nailing) is the standard of care for the treatment of most diaphyseal lower extremity fractures. A few studies have assessed and compared the infection rate following reamed and unreamed IM nailing in open long bone fractures. In the present study, we attempted to compare the infection rate between two procedures in open fractures of tibia. Methods: In this prospective study, we included consecutive patients suffering from open fractures of tibia (Gustilo subtypes II or IIIA) who required IM nailing. Patients younger than 16 years old, other Gustilo types (I, IIIB, and IIIC), fractures reaching to the tibial plateau articular surface, and simultaneous fractures of other bones in the extremity were excluded. All patients were followed up for one year to assess the postoperative infection rate. Results: Of 59 patients, 37 underwent reamed IM nailing and 22 underwent unreamed IM nailing. In reamed group, 4 cases (10.8%) experienced an infection requiring reoperation and antibiotic therapy, while in the unreamed group, it was 5 cases (22.7%). The difference between the groups was not statistically significant. Conclusion: Reamed and unreamed IM nailing procedures for fractures of tibia have similar outcome regarding long-term postoperative infections that require reoperation and antibiotic therapy.