OBJECTIVES: To determine if there is a significant difference in asthma-related health care costs (HCC) and adherence to asthma controllers between patients with asthma and comorbid depressive disorder (A+D) vs. patients with asthma alone (A).  METHODS: Texas Medicaid medical and prescription claims from 1/1/07-10/31/11 were extracted for adults (18-63 years) who had ≥2 asthma controllers in the A group, and additionally ≥2 antidepressants in the A+D group. The index date was the first date of asthma controller use with no previous use in the 6-month pre-index period. Patients were followed for 12 months. HCC (2011 dollars) included asthma-related prescriptions, inpatient, and outpatient costs. Proportion of days covered (PDC) was used to assess adherence, and covariates included asthma-related pre-index HCC, inpatient visit (Yes/No), numbers of outpatient visits and prescriptions, asthma controller class, severity and demographic characteristics. Descriptive statistics, Wilcoxon test and generalized linear model (gamma distribution and log link) were used. RESULTS: Median prescription costs (n=3626) were significantly (p<0.05) higher, while inpatient+outpatient median costs were lower for the A+D vs. A groups ($873.47 vs. $787.28; $47.68 vs. $73.89, respectively). The median (Mean±SD) asthma-related HCC for A group (n=3400) was not significantly different from the A+D group (n=226): [($1038.67, $1349.85±$1140.16) vs. ($1103.70, $1416.49±$1154.57), p=0.2198, respectively]. After controlling for covariates, regression results showed that compared to A group, the A+D group had significantly lower asthma-related HCC (p<0.0001). Asthma controller adherence was significantly and positively related to HCC (p<0.0001). In the A+D group, patients who were more adherent to antidepressants were more adherent to asthma controllers. CONCLUSIONS: Patients with A+D had significantly lower asthma-related HCC than those with A. In A+D, the higher costs of asthma-related prescriptions were offset by the lower costs of inpatient+outpatient claims. Patients with comorbid asthma and depression should adhere to both asthma controller and antidepressant medications.