OBJECTIVES: Asthma is a chronic inflammatory disorder of the airways and the prevalence of asthma has been increasing since the early 1980 across all age, gender and racial groups.  Current asthma treatment guidelines suggest combination therapy of inhaled corticosteroid(ICS) and long acting beta agonist(LABA) for management of moderate to severe asthma.  The primary objective was to identify effects of adherence to combination therapy of LABA and ICS(LABA+ICS) on emergency department(ED) utilization in newly diagnosed asthma patients.  The secondary objective was to identify and use instrumental variables(IVs) to control for sample selection bias. METHODS:   A de-identified patient claims nationwide commercial database was used to identify 7171 patients who were newly diagnosed with asthma.  Patient adherence to LABA+ICS was measured using Medication Possession Ratio(MPR) with two years follow-up.  IVs including medication copay and a binary indicator variable for mail prescription order were tested for over-identification and endogeneity using Sargan test and Hausman specification test.  Differences in ED visit by MPR and adherence group(Poor=MPR<80%, Good=MPR≥80%) were analyzed by Cox proportional hazards model with a linear transformation.  RESULTS: Patients with good adherence were significantly older than poor adherent patients(52 years vs. 48 years, p<0.05) and had significantly higher proportion of mail prescription order as well as medication copay.  Every 1% increase in MPR was associated with a risk of approximately 4% of having an ED visit(HR=3.72, p<0.001) and the risk association for bivariate variable MPR increased from 79% to a two-fold while controlling for gender, age, and comorbidities(HR=2.03, p<0.001).  Only one instrument of proportion of prescription mail order was accepted as the valid instrument and the results demonstrated that every 1% increase in MPR was significantly associated with 4.9% of risk in utilizing ED while holding other covariates constant(p<0.001).  CONCLUSIONS: We found a risk association between high adherence and ED utilization in newly diagnosed asthma patients with LABA+ICS.