Background: Publication and implementation of clinical guidelines is an important educational measure that considerably helps physicians in choosing appropriate antimicrobial drug. Objectives: To evaluate long-term changes in antimicrobial prescribing habits before and after publishing the guidelines and to determine the factors that influence physician's decision to prescribe an antimicrobial drug. Methods: The study among general practitioners in Primorsko-Goranska County was conducted in three periods (January 2009, January 2011 and April 2019) by using a structured questionnaire that included general data about the physician, questions about their habits in antibiotic prescribing, criteria that influenced decision to prescribe antibiotics and antimicrobial agent(s) preferred in treating common infections. Results: Concomitant chronic (non-pulmonary) disease was the most important factor influencing decision to prescribe an antimicrobial drug. Over 88% of physicians that completed the survey declared themselves as rational prescribers of antimicrobials but more than half of them (53.3%) sometimes prescribed an antibiotic even though it was not indicated compared to 75% of self-reported non-rational prescribers (P ˂ 0.05). Self-reported adherence to the guidelines increased from 34.6% in 2011 to 51.8% in 2019. Conclusion: The research showed improvement in physicians' knowledge in choosing the right antibiotic based on the analysis of answers but indicated the necessity for improving communication skills and empowering physicians not to prescribe antibiotics 'just in case' because of diagnostic uncertainty or patient demand. Further qualitative research is needed to understand physicians' prescribing behaviour and decision- making processes in order to develop interventions that will effectively improve the use of antibiotics.