OBJECTIVES: To compare costs associated with short (three-day) versus standard (eight-day) antibiotic therapy in hospitalised adult patients with mild to moderate-severe community-acquired pneumonia (CAP) in an economic evaluation as part of prospective double-blinded randomised controlled trial (RCT). METHODS: Design Randomised, double blind, placebo-controlled non-inferiority trial. Setting Nine secondary and tertiary care hospitals in the Netherlands. Participants 186 adults with a mild to moderate-severe CAP (pneumonia severity index ≤ 110). Patients who had substantially improved after 72 hours (n = 119) were randomly assigned to receive 5 days of either oral amoxicillin or placebo thrice daily. Main outcome measures Direct and indirect medical and non-medical costs associated with resource utilisation during treatment and follow-up until 28 days after randomisation. RESULTS: We randomised 56 patients to placebo and 63 to active treatment. Health outcomes in terms clinical success rates and symptom recovery of were comparable in both study groups. The average cumulative total costs generated during the first 10 days (treatment) were € 3,320 for standard versus € 3,352 for short antibiotic treatment (€32 in favour of standard duration); during the follow-up until day 28 these costs were € 1,072 versus € 879, respectively. The overall difference in costs was € 159 in favour of short therapy (€ 4,391 versus € 4,232, respectively). CONCLUSIONS: Shorter antibiotic treatment is equally effective and does not generate additional costs, as compared to standard treatment in hospitalised patients with mild to moderate-severe CAP who have substantially improved after three days of treatment. Although clinical and economic outcomes for the individual patient are comparable, the relevance of the findings concern the societal level, as a potential reduction in the use of antibiotics may slow down the development of antibiotic resistance and need for costly development of new antibiotic therapies.