We evaluated the immunogenicity of a reduced-dose intradermal trivalent, inactivated, split-virion seasonal influenza vaccine compared to that of a conventional intramuscular vaccination in chronic obstructive pulmonary disease (COPD) patients. One hundred and fifty-six COPD patients randomly received either 0.2 ml (6 microg hemagglutinin (HA) per strain) split into two-site intradermal (ID) injections or a single 0.5 ml (15 microg HA per strain) intramuscular (IM) injection. Geometric mean titers, seroconversion factors, seroconversion rates and seroprotection rates at 4 weeks post-vaccination in the ID group were less than those in the IM group. Only the seroconversion factor to influenza B in the ID group was statistically less than in the IM group (18.8 in the ID group, n=81 versus 37.3 in the IM group, n=75, p=0.045). Nevertheless, each strain of the ID vaccination met all the Committee for Proprietary Medicinal Products (CPMP) criteria. Seroprotection rates were above 60% throughout the year in influenza A (H3N2), for at least 6 months in influenza A (H1N1) and at least 4 weeks in influenza B in both ID and IM groups. The reduced-dose intradermal vaccination may be considered for use in COPD patients in a vaccine shortage situation.