Premature interruption of dual oral antiplatelet therapy is an issue of increasing importance, and is particularly critical for at least three major reasons. First, patients eligible for temporary dual oral antiplatelet therapy are at high risk of acute recurrent thrombosis because they underwent a recent drug-eluting stent implantation or they experienced a recent acute coronary syndrome. Secondly, the proportion of these patients is now increasing and definite guidelines on how to manage interruption do not exist. Lastly, there is now evidence that premature interruption of oral antiplatelet therapy can lead to recurrence of events, with a significant impact on outcome in these high-risk patients. A perceived risk of increased bleeding events often leads to the interruption of oral antiplatelet therapy, but in many instances, the interruption is unjustified. Whether premature interruption of oral antiplatelet therapy is appropriate, and whether alternative therapies should be substituted are two important questions that, to date, remain unresolved. It is unlikely that the issue of premature withdrawal of dual oral antiplatelet therapy in high bleeding risk situations will ever be solved by randomized studies. Indeed, there is an urgent need to define an evidence-based strategy for the management of oral antiplatelet therapy in the peri-operative period. The risks of bleeding and ischaemic events, and the need to interrupt oral antiplatelet therapy, need to be evaluated for common situations such as dental care, or fibroscopic examination of the digestive tract.