This trial is a randomized, double-blind, parallel-group, multicenter study to be conducted in the United States. The purpose of the study is to evaluate the rate of exacerbations of chronic obstructive pulmonary disease (COPD) following hospital discharge for an acute exacerbation of COPD, in patients receiving either fluticasone propionate/salmeterol combination product 250/50mcg BID or salmeterol 50mcg BID via DISKUS™ over 29 weeks. The study population will include patients hospitalized for an acute exacerbation of COPD. The target enrolment is 720 subjects at 80 study centers. The primary endpoint is the rate of exacerbation requiring hospitalization that occur more than 21 days post-discharge, emergency room visit or physician's office visit for an exacerbation of COPD requiring treatment with oral corticosteroids or oral corticosteroids and antibiotics. The secondary endpoint is the rate of COPD exacerbation requiring treatment with oral corticosteroids, antibiotics, and/or hospitalization (alone and in combination). Related efficacy endpoints include, time to first exacerbation of COPD requiring treatment with oral corticosteroids, antibiotics, and/or hospitalization (alone and in combination), pre-dose AM FEV1, the probability of premature withdrawal of subject from the study, and supplemental albuterol use, change in biomarkers of inflammation, including, surfactant protein D (SP-D), clara cell secretory protein 16 (CC-16) and high sensitivity C-reactive protein (hs-CRP). Health outcome assessments include domain scores evaluation for fatigue, dyspnea, emotional function and mastery, measured with the Chronic Respiratory Disease Questionnaire self-administered standardized format (CRQ-SAS); and symptoms (congestion, cough, phlegm, mucus, chest discomfort, shortness of breath and sleep disturbance), assessed by the EXAcerbations of Chronic pulmonary disease Tool (EXACT). Albuterol will be supplied to study subjects for use as-needed throughout the study. Safety will be assessed by monitoring of adverse events.