Combination treatment with a beta-lactam plus a macrolide may improve the outcome for elderly patients with community-acquired pneumonia (CAP). The prognoses and mortality rates for elderly patients with CAP who receive ceftriaxone combined with a 3-day course of azithromycin or a 10-day course of clarithromycin were compared in an open-label, prospective study. Of 896 assessable patients, 220 received clarithromycin and 383 received azithromycin. There were no significant differences between groups with regard to the severity score defined by the Pneumonia Patient Outcomes Research Team (PORT) study group; the incidence of bacteremia was also not significantly different. However, for patients treated with azithromycin, the length of hospital stay was shorter (mean+/-SD, 7.4+/-5 vs. 9.4+/-7 days; P<.01) and the mortality rate was lower (3.6% vs. 7.2%; P<.05), compared with those treated with clarithromycin. There might be a difference in the outcome for patients with CAP depending on the macrolide used. A shorter treatment course with azithromycin may result in better compliance with therapy.