OBJECTIVE: To estimate health care costs for the treatment of acute exacerbation of chronic bronchitis (AECB) and community-acquired pneumonia (CAP) in 4 previously-reported Phase III multinational comparative trials of telithromycin vs amoxicillin-clavulanic acid and clarithromycin in Canada. METHODS: In each of the 4 studies, patients were followed for 1 month and the primary endpoint was clinical efficacy at the posttherapy/test of cure (TOC) visit. Each trial prospectively collected data on study indication-related hospitalizations, additional health care provider visits, and additional antibiotic therapy. Three trials also collected information on additional laboratory and other tests and procedures. Cost analyses were performed from the perspective of the Ontario Ministry of Health. RESULTS: A total of 1045 and 853 patients in the 4 trials were randomized to receive telithromycin or a comparator, respectively. At baseline, the patient groups were similar with respect to demographic and clinical characteristics. The clinical efficacy of telithromycin and the comparators was similar in each study. Compared to patients randomized to comparator, those randomized to telithromycin were less likely to require AECB- and CAP-related hospitalization. Total and average costs of care were approximately 2 to 3 times higher in the comparator groups, driven by higher hospitalization rates. The ratio of average total treatment cost per patient in each comparator to that of telithromycin was as follows: $40/$19=2.1 for amoxicillin-clavulanic acid in AECB; $241/$122=1.9 for clarithromycin in AECB; $198/$109=1.8 and $293/$90=3.3, for clarithromycin in CAP. CONCLUSION: Although clinical cure rates for telithromycin, amoxicillin-clavulanic acid, and clarithromycin are comparable, health care costs appear to be lower among patients taking telithromycin, a finding driven by fewer hospitalizations. Since hospitalization accounts for a major proportion of the direct health care costs associated with AECB and CAP in Canada, the use of telithromycin may significantly reduce the total costs of care for these respiratory conditions.