This before–after study aimed to evaluate the effect of two interventions on lowering the prescription of antibiotics in lower respiratory tract infections (LRTI) in Spain.General practitioners (GPs) registered all cases with LRTIs over 3-week periods before and after an intervention, in 2008 and 2009. Two types of intervention were considered: full-intervention group (FIG), consisting of discussion sessions of the results of the first registry, courses for GPs, guidelines, patient information leaflets, workshops on rapid tests and use of the C-reactive protein (CRP) test; GPs in the partial-intervention group (PIG) underwent all of the above interventions except for the workshop on rapid tests, and they did not have access to CRP. A multilevel logistic regression analysis was performed considering the prescription of an antibiotic as the dependent variable.210 physicians were assigned to FIG and 70 to PIG. In 2009, 58 new physicians were included as a control group. 5,385 LRTIs were registered. Compared with the control group, the OR of antibiotic prescription after the intervention in the PIG was 0.42 (95% CI: 0.22–0.82) and 0.22 (95% CI: 0.12–0.38) in the FIG.Intervention led to a reduction in the prescription of antibiotics, mainly when CRP testing was available.