To determine the cost-effectiveness and cost-benefit of influenza vaccination in chronic obstructive pulmonary disease (COPD) patients the authors conducted a stratified randomized, double-blind, placebo-controlled trial from June 1997 to November 1998 at a university hospital in Thailand. A total of 125 COPD patients were stratified based on their FEV1 as mild COPD (FEV1 > or = 70% predicted), moderate COPD (FEV1 50-69% predicted) and severe COPD (FEV1 < 50% predicted) and in each severity stratum they were randomized to the vaccine group (received intramuscular injection with purified trivalent split-virus vaccine containing A/Texas/36/91 (H1N1), A/Nanchang 1933/95 (H3N2) and B/Harbin 107/94) or the placebo group (received intramuscular injection with vit B1). Number of episodes of acute respiratory illness (ARI) related to influenza (clinical ARI + a serum hemagglutination inhibition antibody titre of 38 or greater and a four fold titre increase in convalescent serum compared to acute serum) as well as severity of each ARI (outpatient treatment, hospitalization or required mechanical ventilation) and costs of treatment (direct medical costs comprised real drug costs from the hospital dispensary in outpatient cases and real charges in hospitalization cases) were collected and analyzed for the cost-effectiveness and cost-benefit of influenza vaccination. The incidence of influenza-related ARI in the study year was 27 per cent in the placebo group and 6.4 per cent in the vaccine group (relative risk [RR] 0.24, vaccine effectiveness 76%). The incidence was 27.3 per cent, 23.5 per cent and 29.2 per cent in mild, moderate and severe COPD respectively in the placebo group and 4.3 per cent, 12.5 per cent, and 4.3 per cent in the mild, moderate and severe COPD respectively in the vaccine group (RR 0.16, 0.53 and 0.15; vaccine effectiveness 84%, 47%, and 85% respectively). The incremental cost-effectiveness ratios demonstrated that for every 100 patients with mild COPD whom the authors decided to vaccinate, the cost would be 24,840 baht more and would prevent 18.2 outpatients, 4.8 hospitalizations and 0 patient from mechanical ventilation due to ARI related to influenza. Likewise, the authors would have prevented 5.1 outpatients, 5.9 hospitalizations, 5.9 mechanical ventilation and 20.8 outpatients, 3.9 hospitalizations, 8.3 mechanical ventilation for every 100 moderate COPD and every 100 severe COPD patients vaccinated respectively. More than 90 per cent of the costs of treatment of influenza-related ARI were costs of hospitalization and for patients with moderate and severe airflow obstruction, more than 90 per cent of these costs were attributed to the costs of treating the patients who required mechanical ventilation. Predicted cost savings for every 100 mild COPD, 100 moderate COPD and 100 severe COPD patients vaccinated were 125,629 baht, 538,184.3 baht, and 680,647.1 baht respectively. In conclusion: Influenza vaccination is highly effective in the prevention of acute respiratory illness related to influenza virus infection in COPD, regardless of severity of airflow obstruction. Vaccination is more cost-effective in preventing mechanical ventilation episodes and more cost-benefit in patients with more severe airflow obstruction. Influenza vaccination should be recommended to all patients with COPD with the higher priority provided to patients with more severe airflow obstruction.