Resistance increases with the use and abuse of antibiotics. Since physicians are primarily responsible for the decision to use antibiotics, ascertaining the attitudes and knowledge that underlie their prescribing habits is thus a prerequisite for improving prescription. Three-year follow-up cohort study (2008-2010) targeting primary-care physicians (n = 2100) in Galicia, a region in NW Spain. We used data obtained from a postal survey to assess knowledge and attitudes. A physician was deemed to have demonstrated Appropriate Quality Prescription of Antibiotics (dependent variable) in any case where half or more of the indicators proposed by the European Surveillance of Antimicrobial Consumption had values that were better than the reference values for Spain. The mail-questionnaire response rate was 68·0% (1428/2100). The adjusted increase in the interquartile OR of displaying good prescribing of antibiotics for each attitude was: 205% for fear ("When in doubt, it is better to ensure that a patient is cured of an infection by using a broad-spectrum antibiotic"; 95%CI: 125% to 321%); 119% for better knowledge ("Amoxicillin is useful for resolving most respiratory infections in primary care"; 95%CI: 67% to 193%); and 21% for complacency with patients' demands ("Antibiotics are often prescribed due to patients' demands"; 95%CI: 0% to 45%). Due to the fact that physicians' knowledge and attitudes are potentially modifiable, the implementation of purpose-designed educational interventions based on the attitudes identified may well serve to improve antibiotic prescription.