More than 10 years after its appearance in clinical practice, laparoscopic cholecystectomy can now be considered the standard operation for gallstone disease. However, some aspects of this operation are still debated. The need to perform routine antibiotic prophylaxis in order to reduce the incidence of infectious complications is still a matter of controversy. International guidelines do not recommend its routine use. The evidence for this, however, is rather limited, because there are no randomized trials with a sufficient number of cases to avoid a type II error. The authors, on behalf of the Lap Group Roma, introduce the protocol of a multicenter prospective randomized controlled clinical trial designed to find a definitive answer to this problem.