BACKGROUND: Many interventions aimed at improving the quality of antibiotic prescribing have been investigated, but more knowledge is needed regarding the impact of different intensity interventions. OBJECTIVES: To compare the effect of two interventions, a basic intervention (BI) and intensive intervention (II), aimed to improve the adherence to recommendations on first-line antibiotics in patients with respiratory tract infections (RTIs). METHODS: General practitioners (GPs) from different regions of Spain were offered two different interventions on antibiotic prescribing. They registered all patients with RTIs during 15 days before (2008) and after (2009) the intervention. GPs in Catalonia were exposed to BI including prescriber feedback, clinical guidelines and training sessions focused on appropriate antibiotic prescribing. The other group of GPs was exposed to an II, which besides BI, also included training and access to point-of-care tests in practice. RESULTS: The GPs registered 15 073 RTIs before the intervention and 12 760 RTIs after. The antibiotic prescribing rate reduced from 27.7% to 19.8%. Prescribing of first-choice antibiotics increased after the intervention in both groups. In the group of GPs following the BI, first-line antibiotics accounted for 23.8% of antibiotics before the intervention and 29.4% after (increase 5.6%, 95% confidence interval (CI): 1.2-10%), while in the group of GPs following the II these figures were 26.2% and 48.6% (increase 22.4%, 95% CI: 18.8-26%), respectively. CONCLUSION: Multifaceted interventions targeting GPs can improve adherence to recommendations for first-line antibiotic prescribing in patients with RTI, with intensive interventions that include point-of-care testing being more effective.