ObjectivesIn France, 75% of systemic antibiotics are prescribed by general practitioners (GPs) in primary care. We aimed to estimate the burden of inappropriate use related to excessive prescription duration. Patients and methodsIn 2021, we performed a cross-sectional and pharmaco-economic study of a network of six GPs. The references for optimal durations were those of the French national guidelines for antibiotic prescription. ResultsOut of 196 antibiotic prescriptions, 33.7 % were of excessive duration, with a mean excess of 0.9 [0.86–0.94] to 1.6 [1.45–1.72] days per prescription. Ear, nose, and throat, respiratory tract, and skin and skin structure infections were the main infections associated with excessive prescription. The pharmaco-economic analysis showed that the cost of excessive prescription duration would range from an estimated 151 to 262 million € in France in 2021. ConclusionAddressing excessive antibiotic prescription duration by GPs may represent a powerful and cost-saving tool in antimicrobial stewardship programs.