Adherence to asthma treatment may not completely prevent exacerbations. Clinical trial results indicate that many highly adherent asthma patients still have symptoms. Little is known about the level of control achieved by adherent patients outside clinical trials. This study was designed to evaluate the extent of asthma control among insured patients who were highly adherent to combination controller therapy. We used an administrative claims database for this cohort study of patients aged 12-64 years. Patients were newly treated with fluticasone, 500 micrograms/salmeterol, 50 micrograms, between January 1, 2003 and June 30, 2004. Patients were stratified according to adherence levels: low (<50%), moderate (50-74%), and high (> or =75%). We compared rates of poor control. A logistic regression model was used to control for baseline differences. Among 3357 patients, the mean age was 40.5 +/- 13.6 years, and 64.1% were women. Sixty-one percent had low adherence, 20% had moderate adherence, and 19% had high adherence. Highly adherent patients were older, and more used fluticasone, 250 micrograms/salmeterol, 50 micrograms, during the preindex period than the other groups. Even after starting high-dose fluticasone/salmeterol, many patients with low, moderate, and high adherence had indicators of poor symptom control (28.9% [587/2030], 30.6% [209/682], and 30.7% [198/645], respectively). Patients who were highly adherent and used additional controller medications had rates of poor control that ranged from 23.1 to 31.2%. After adjusting for age, gender, and baseline characteristics, results were similar. Many patients continue to have poor asthma control despite being adherent to high-dose combination therapy or using additional controller medications.