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Background: Colorectal surgery has some of the highest infection rates among elective operations. Decades of research have not resolved the controversy surrounding prophylactic antibiotic regimens, whether oral and/or intravenous, for colorectal surgery. Recent studies have shown that fewer surgeons are using scheduled oral antibiotics the day before surgery. Many published guidelines suggest the use of intravenous antibiotics only, despite the fact that data demonstrates lower infection rates when oral antibiotics are used, especially in combination with intravenous antibiotics. Some authors have begun to reexamine prophylactic oral antibiotic regimens and are renewing the debate on their efficacy at reducing infection-related complications following colorectal surgery. Methods: A critical review of the literature over the past six decades was undertaken. Results: Results from studies over the past six decades demonstrate statistically significant reductions or trends towards lower infection-related complications in colorectal surgeries among patient groups receiving preoperative prophylactic oral antibiotics or a combination of preoperative oral and intravenous antibiotics. Conclusions: Sufficient evidence exists that demonstrates combination therapy of scheduled preoperative oral and intravenous antibiotics results in the lowest rate of infection-related complications, despite the fact that scheduled oral antibiotics the day before colorectal surgeries has fallen out of favor with many surgeons. Furthermore, the combination of neomycin and erythromycin make an ideal prophylactic regimen because of their high concentrations in the colon, low cost, low resistance rate, and availability, in addition to the convincing evidence throughout the literature describing their ability at lowering infectious complications following colorectal surgery

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