OBJECTIVES:  To evaluate adherence to 5-aminosalicylate (5-ASA) therapy and its association with health-related quality of life (HRQoL) and health care resource utilization in inflammatory bowel disease (IBD). METHODS:  This was a retrospective study. Data were drawn from the Household Component of the Medical Expenditure Panel Survey (MEPS-HC) for 2010-2014 (178,948 yearly observations). Analysis was limited to data for adults who were identified with IBD (ICD 9 code of 555/556), received 5-ASA for IBD, and were in-scope during all rounds of MEPS-HC. Adherence was quantified as the proportion of days covered (PDC); a PDC ≥0.80 was classified as adherent. HRQoL was assessed with SF-12. Descriptive statistics were calculated, association were analyzed with generalized linear models. RESULTS:  The study sample consisted of 94 yearly observations (mean±SD age: 49.72±15.79, female: 57.45%); 73.40% of observations were from nonadherent patients. Crude and age-sex adjusted results indicated that adherence to 5-ASA had a significant association with SF-12 Mental Component Summary (CS) score (both P<0.01); in age-sex adjusted analysis the mean difference was 5.81 (95% CI: 1.85-9.77) between adherent and nonadherent patients. Neither analysis found relationship between adherence and SF-12 Physical CS score. For the number of yearly emergency room (ER) visits, crude analysis showed significant association with adherence (yearly ER visit rate ratio in the adherent sample was 31.54% of the rate of the nonadherent sample; 95% CI: 0.10-1.02; P=0.05); its effect was not significant after controlling for age, sex and insurance coverage. In crude and age-sex-insurance adjusted analyses adherence had a significant effect on the number of yearly hospitalizations (both p<0.01); no hospitalization occurred in the adherent sample. Adherence showed no relation with yearly number of outpatient visits. CONCLUSIONS: Adherence to 5-ASA therapy is poor among adults with IBD. Mental component of HRQoL, and frequency of ER visits and hospitalization are strongly associated with adherence to 5-ASA in IBD.