A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether clopidogrel rather than aspirin plus a proton-pump inhibitor reduce the frequency of gastrointestinal complications after cardiac surgery. Altogether 40 publications were identified using the below-mentioned search and all the papers reference lists were searched. Six papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group, relevant outcomes and weaknesses were tabulated. We conclude that clopidogrel causes fewer gastrointestinal complications than aspirin in those patients with no previous history of gastric or duodenal ulceration with a number needed to treat of around 200 to prevent an episode of bleeding per year. However, in those patients with a previous history of gastrointestinal complications, clopidogrel alone is not a safer alternative than aspirin alone. Either aspirin or clopidogrel combined with a proton pump inhibitor are equally effective for these patients.