OBJECTIVES: To compare the clinical and economic impact of oral TEL and CLA in adult outpatients with CAP. METHODS: In 2 independent, randomized, double-blind, multicenter clinical studies, 1023 adult outpatients (Study 1, n=448; Study 2, n=575) with CAP received TEL 800 mg once daily for 10 (Study 1) or 5 or 7 days (Study 2), or CLA 500 mg twice daily for 10 days (comparator regimen, both studies). Clinical and economic outcomes were followed for four weeks. The primary statistical hypothesis was equivalence of clinical efficacy (per-protocol populations). Economic outcomes in the intent to treat populations were assessed by non-protocol-driven CAP-related resource use. Unit costs were assigned as follows (Study 1/2): additional antibiotics/medications using 1999/2000 Redbook average wholesale prices; physician visits/tests/procedures using Medicare's Resource Based Relative Value Scale; and hospitalizations using 1999/2000 American Hospital Association national average daily rates for short-term hospitalization. Data from the two studies were pooled and analyzed. RESULTS: The clinical efficacy of TEL and CLA was equivalent (88.8% [428/482] vs 90.1% [272/302], respectively). Patients treated with TEL had fewer CAP-related hospitalizations vs CLA patients (13/612 [2.6%] vs 15/411 [3.6%], respectively). The length of stay in hospital was shorter for TEL vs CLA patients (16.8 vs 33.8 hospital days per 100 patients, respectively). Concomitant antibiotics were required by 135/612 (22.1%) TEL vs 110/411 (26.8%) CLA patients. The average per-patient cost of additional resource use for TEL ($309) was considerably less than that for CLA ($622), with per-patient savings of $313 for TEL. Greater savings were observed for the subset of patients aged 65 years: average per-patient cost of additional resource use for TEL of $305 vs $896 for CLA, with per-patient savings of $591 for TEL. CONCLUSIONS: TEL is an effective therapy for outpatients with CAP and is associated with lower direct healthcare costs than CLA.