OBJECTIVES: To evaluate differences in medication compliance and persistence between patients with persistent (HP) and intermittent or non-persistent (HNP) asthma according to the Health Plan Employer Data and Information Set (HEDIS) definitions, as well as among the classes of asthma medications. METHODS: A retrospective cohort analysis of the Integrated Healthcare Information Services (IHCIS) administrative database evaluated patients >/=5 years of age with at least 2 prescriptions of asthma medication. Asthma severity was classified as HP (n=21,698) or HNP (n=11,967), in accordance with 2006 HEDIS criteria; compliance, calculated as medication possession ratios (MPR) and persistence, calculated as days supply before discontinuation, switching, or augmentation, were measured in patients treated with inhaled corticosteroids (ICS) (n=3906 HP, n=3856 HNP), leukotriene modifiers (LM) (n=10,005 HP, n=3823 HNP), and ICS+LABA combinations (n=5893 HP, n=3538 HNP) over a 1-year period. The study groups' comparisons were conducted using t-test or analysis of variance where appropriate. RESULTS: Overall, HP patients had higher MPRs with all categories of medication (71+29%) compared with HNP patients (43+27%, p<0.001). Oral LM (78+27% HP, 51+29% HNP) were taken more frequently than ICS (55+30% HP, 31+21% HNP) or ICS+LABA combinations (65+28% HP, p<0.001, 43+25% HNP, p<0.001). Persistence was longer for LM (139+110 days HP, 90+86 days HNP), than for ICS (64+72 days HP, 37+32 days HNP), or ICS+LABA (106+108 days HP, 66+73 days HNP, p<0.001 for both). CONCLUSION: Both compliance and persistence remained suboptimal in this large asthmatic population, with HNP patients far less consistent with their medication dosing and duration of use than HP patients. LMs were used more consistently than inhaled medications, with ICS being the least consistently used asthma medication. Additional measures are needed to improve compliance and persistence with these medications.