A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether prophylactic therapy with antioxidant vitamins reduces the incidence of postoperative atrial fibrillation (AF). One hundred and fifty-four papers were found using the reported search, of which five were judged to represent the best evidence to answer the question. The authors, journal, date, country of publication, patient group studied, study type, relevant outcomes and results were tabulated. Four of the five studies found antioxidant vitamins to significantly reduce the incidence of postoperative AF. Two of the studies show that prophylactic treatment with adjuvant vitamin C and β-blockers is more effective than β-blocker therapy alone. The quality of these studies was assessed using a Jadad scoring system, which identified four of the studies to be of low and one to be of high methodological quality. We conclude that although preliminary evidence suggests that prophylactic antioxidant vitamins may be effective in reducing the incidence of postoperative AF, there is a lack of high-quality data. Additional large-scale, adequately powered clinical studies are warranted before antioxidant vitamins can be considered for routine use in this setting.