Guidelines have been developed to improve the treatment of community-acquired pneumonia (CAP) but information regarding their influence on costs is lacking. The aim of the present study was to conduct a cost-effectiveness analysis of CAP treatment from the hospital perspective when adhering to Spanish guidelines. A prospective cohort study was performed in 271 patients with CAP admitted to a tertiary-care hospital, not needing intensive care. Collected data included patients' characteristics, comorbidity, initial risk class, resource use (medication, blood and microbiological analyses, and radiology) and economic data. Antimicrobial treatment was recorded as adherent or nonadherent to Spanish guidelines. Outcome measures were mortality and readmission at 30 days. The median cost for adherent treatment was 1,665.5 versus 1,710.5 Euros for nonadherent treatment. Mortality and readmission were 10% and 2.1% for adherent treatment versus 13.6% and 6.2% for nonadherent treatment. The cost-effectiveness ratio was 2,277 Euros per expected cure for patients treated according to the guidelines and 2,567 Euros per expected cure for the nonadherence group. The incremental cost-effectiveness ratio showed that adherence to treatment guidelines saved 1,121 Euros per patient cured compared with nonadherence. The sensitivity analysis demonstrated that the findings were robust. An antimicrobial treatment according to guidelines is the dominant alternative due to its cost-effectiveness.