A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether prophylactic Amiodarone can safely reduce the incidence of atrial fibrillation (AF) post-cardiac surgery. Altogether 90 papers were found using the reported search, of which 12 presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that there is strong evidence that both oral and intravenous Amiodarone given prophylactically reduces the incidence of post-operative AF, with a number needed to treat of only seven to prevent an episode of AF.