Objectives: In 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 methods: In 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. Results: Out 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 <euro> in France in 2021. Conclusion: Addressing excessive antibiotic prescription duration by GPs may represent a powerful and cost- saving tool in antimicrobial stewardship programs.