BackgroundAlthough the interest of antibiotics is well known, antibiotics prescription is associated with side effect, especially in patients with multiples comorbidities. One way to reduce the incidence of side effects is to respect antibiotics prescriptions guidelines. Our objective was to investigated the factors associated with guidelines adherence in elderly patients with multiples comorbidities.MethodsFrom October 2015 to December 2016, antibiotics prescription and guidelines adherence were analyzed in two post-acute care and rehabilitation services of a 2600-bed, university-affiliated center.ResultsOne hundred and twenty-eight patients were included, fifty-nine (46%) patients had antibiotics prescription according to guidelines. In Multivariable logistic regression analysis, prescription of 2 antibiotics or more (OR = 0.168, 95% IC = 0.037–0.758, p < 0.05), 85 years of age and more (OR = 0.375, 95% IC = 0.151–0.931, p < 0.05) and the Charlson comorbidity index score (OR = 0.750, 95% IC = 0.572–0.984, p < 0.05) were negatively associated with antibiotics prescriptions according to guidelines.ConclusionsHigh comorbidity in the elderly was negatively associated with the guidelines adherence of antibiotiсs prescriptions. These criteria should be considered to optimize antibiotics prescriptions in elderly patients.Electronic supplementary materialThe online version of this article (10.1186/s12877-019-1265-1) contains supplementary material, which is available to authorized users.