OBJECTIVES: There is inconclusive evidence on the advantages of branded levalbuterol over generic albuterol.  This study is the first to examine the use and spending of these two short-acting beta agonists in a nationally representative sample of Medicare patients with COPD enrolled in Medicare Part D.  The study also examines patient characteristics associated with levalbuterol use and compares the use of other Medicare Parts B and D covered COPD medications among albuterol and levalbuterol users.  METHODS: Data were obtained from the 2005-2006 5% Medicare files linked to the 2006 Medicare Part D files.  The sample consisted of all fee-for-service beneficiaries with COPD enrolled in stand-alone Part D plans in 2006.  Patient characteristics and other COPD medication use were compared across albuterol-only users, levalbuterol-only users, and users of both medications.  Multinomial logistic regressions identified the independent factors associated with levalbuterol use.   RESULTS: There were 5.5 times more albuterol users than levalbuterol users; yet total spending on levalbuterol was $169 million whereas on albuterol was $50 million in 2006.  Levalbuterol-only users were more likely to be older, sicker, and reside in the South than albuterol-only users.  Part B covered nebulizer formulations were more frequently used among levalbuterol-only users whereas albuterol-only users were more likely to use inhalers under Part D. CONCLUSIONS: Our findings on the striking differences between levalbuterol and albuterol users in terms of spending, patient characteristics, geographic region, and drug formulation/device type call for further investigations into these issues as well as comparative effectiveness and cost-effectiveness studies of these agents.