OBJECTIVES: Clinical trials of chronic obstructive pulmonary disease (COPD), a progressive disease with a substantial economic burden, primarily assess exacerbation rates based on health resource utilization (HRU), leading payers to focus on this endpoint as a cost driver. The drug approval process often requires documentation of clinically relevant improvements in measures such as forced expiratory volume in one second (FEV); however, their link to longer-term outcomes, such as exacerbations and HRU are not known. We conducted a systematic review of the published literature to evaluate the linkage. METHODS: We searched MEDLINE- and Embase-indexed English-language publications from 2002 through October 1, 2014 for randomized controlled trials with ≥20 adult patients with COPD.  Included trials described changes in FEVor St. George’s Respiratory Questionnaire (SGRQ), as well as exacerbations or HRU. RESULTS: We identified 13 trials among 1,196 publications reporting changes in SGRQ or FEV and rate of exacerbation and hospitalization.  We combined FEV pre-bronchodilator values with FEVtrough values given the similarity of these variables. Based on the MCID value for SGRQ of 4 units, exacerbations ranged from 0.414 to 5.61/person-year among those not reaching SGRQ MCID, compared with a range of 0.42-1.07/person-year among those reaching SGRQ MCID. Using a minimal clinically important difference (MCID) value for FEV of 100mL, the exacerbation rate ranged from 0.414 to 5.61/person-year among those not reaching FEV MCID, compared to 0.69 to 1.02/person-year among those reaching FEVMCID.  The annual hospitalization rate due to exacerbations ranged from 0.02-0.7/person-year among those not reaching SGRQ MCID, and from 0.03-0.16/person-year among those reaching SGRQ MCID.  Annual hospitalization rates due to exacerbations ranged from 0.02-0.7/person-year among those not reaching FEV MCID, compared to 0.05-0.16/person-year among those reaching FEVMCID.  CONCLUSIONS: Preliminary results suggest a relationship between clinically meaningful improvements in bronchodilation and patient-reported outcomes and annualized exacerbations and hospitalizations.