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Background:Irrational antibiotic prescribing as a global health problem has a major influence on medical care quality and healthcare expenditure. This study was aimed to determine the pattern of antibiotic use and to assess the seasonality and physician-related factors associated with variability in antibiotic prescribing in Isfahan province of Iran.Methods:This cross-sectional survey was conducted on all prescriptions issued by general physicians from rural and urban areas in 2011. Associations between season of prescribing and physician-related variables including gender, practice location and time since graduation with antibiotic prescriptions and also the pattern of antibiotic prescribing were assessed using Chi-square tests and multiple logistic regression models.Results:Of the 7439709 prescriptions issued by 3772 general practitioners, 51% contained at least one antibiotic. Penicillins were the most frequently prescribed antibiotics, followed by cephalosporins and macrolides. Over-prescription of penicillins was associated with female gender (odds ratio [OR], 2.61; 95% confidence interval [CI] 2.13–3.19) and with moderate duration of time in practice (10–20 years) (OR, 1.42; 95% CI 1.14–1.76). Higher rates of cephalosporins prescription were observed in urban areas than rural areas and by male physicians. Seasonal peak was detected for penicillins and cephalosporins prescriptions in autumn.Conclusions:These findings showed the widespread use of antibiotics by general practitioners that was associated with the physicians’ gender, time since graduation and practice location and also season of prescribing. More researches are needed on other factors related to the overprescribing of antibiotics and they could be used to project educational programs for improvement of antibiotic prescribing quality in our country.