OBJECTIVE: To conduct a benefit-risk assessment comparing telithromycin with other commonly prescribed therapies for the treatment of community-acquired pneumonia (CAP). METHODS: We developed a model to quantify the benefits and risks of telithromycin versus other common therapies for CAP in terms of quality-adjusted days (QAD) gained. A typical 65-year-old patient was assumed to receive amoxicillin, clarithromycin, or telithromycin for the treatment of acute CAP. Drug efficacy, drug resistance, adverse event (AE) rates and sequelae, and utility decrements associated with CAP and AEs were estimated from published clinical trials and other secondary sources. Benefits of telithromycin versus other therapies were assessed by estimating the gain in QAD due to successful treatment of CAP. Risks were assessed by estimating the QAD lost due to treatment-related AEs (liver toxicity, prolonged QT interval, diarrhea, and blurry vision) and their sequelae. The net benefit of telithromycin was calculated by summing expected benefits and risks over the 21-day period after treatment initiation (including lifetime QAD lost due to death and chronic conditions). We used a second-order Monte Carlo simulation to evaluate the effect of uncertainty in key model parameters on our findings. RESULTS: Patients treated with telithromycin versus amoxicillin are expected to gain 31.01 QAD due to successful treatment of CAP and 0.26 QAD due to AEs. Versus clarithromycin, telithromycin patients lose 0.01 QAD to AEs; however, the net benefit is a gain of 13.09 QAD. Probabilistic sensitivity analyses showed telithromycin to be at least as beneficial as amoxicillin and clarithromycin in 85% and 68% of 10,000 iterations, respectively. CONCLUSIONS: Telithromycin demonstrated a net benefit in terms of QAD gained versus both amoxicillin and clarithromycin despite slightly higher risks due to AEs than clarithromycin. In general, QAD lost due to AEs were negligible compared to the potential benefits from successful treatment of CAP with telithromycin.