Background: Low-molecular-weight heparin (LMWH) appears to be safe and effective for treating pulmonary, embolism (PE), but its cost-effectiveness has not been assessed. Methods: We built a Markov state-transition model to evaluate the medical and economic outcomes of a 6-day course with fixed-dose LMWH or adjusted-dose unfractionated heparin (UFH) in a hypothetical cohort of 60-year-old patients with acute submassive PE. Probabilities for clinical outcomes were obtained from a metaanalysis of clinical trials. Cost estimates were derived from Medicare reimbursement data and other sources. The base-case analysis used an inpatient setting, whereas secondary analyses examined early discharge and outpatient treatment with LMWH. Using a societal perspective, strategies were compared based on lifetime costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio. Results: Inpatient treatment costs were higher for LMWH treatment than for UFH ($13,001 vs $12,780), but LMWH yielded a greater number of QALYs than did UFH (7.677 QALYs vs 7.493 QALYs). The incremental costs of $221 and the corresponding incremental effectiveness of 0.184 QALYs resulted in an incremental cost-effectiveness ratio of $1,209/QALY. Our results were highly robust in sensitivity analyses. LMWH became cost-saving if the daily, pharmacy, costs for LMWH were <$51, if >= 8% of patients were eligible for early discharge, or if >= 5% of patients could be treated entirely, as outpatients. Conclusion: For inpatient treatment of PE, the use of LMWH is cost-effective compared to UFH. Early, discharge or outpatient treatment in suitable patients with PE would lead to substantial cost savings.