Background: Responsible antibiotic stewardship requires surgeons treating open fractures to use the narrowest appropriate antibiotic coverage possible to prevent infection. Because inter-observer agreement about the application of the Gustilo-Anderson open fracture classification is moderate at best, antibiotic selection can be overly aggressive. The purpose of this study was to evaluate the outcomes of Type II open fractures treated with gram-positive coverage only (GP) versus broad-spectrum antibiotic coverage (BS) with piperacillin-tazobactam (PT). Methods: A retrospective review of all Type II open fractures was performed at a single Level one trauma center over a 5-year period (2013-2017). All patients received prophylactic antibiotics on arrival on the basis of the best judgment of classification by the house officer on call. The final Gustilo-Anderson open fracture classification was assigned intra-operatively by the operating surgeon. Two groups were created, a GP antibiotic group (cefazolin and/or clindamycin) and a BS group (PT). A minimum of 3-month follow-up was required for inclusion. Patient demographics, cost of treatment, fracture-related infection (FRI) rates, and infecting bacteria were assessed. Results: The GP group contained 70 open fractures and the BS group contained 74 open fractures. Between the groups, there were no differences in age, sex, race, Body Mass Index, American Society of Anesthesiologists Class, or smoking status. There were no statistical differences in Injury Severity Score (ISS), fracture location, fixation method, or rates of staged management with external fixation. There was no difference in FRI rate between the GP and BS groups (8.6% versus 10.8%; p = 0.78). The bacteria responsible for FRI were similar in the GP and BS groups. The hospital charge for PT was 4.39 × the cost of cefazolin. Conclusions: The use of BS coverage in Type II open fractures does not result in a lower infection rate and adds significant cost to patient care. These data support the use of a GP-only antibiotic regimen for Type II open fractures.