OBJECTIVE: To develop and evaluate a self-report clinical and research adherence barrier survey designed to screen for specific barriers to adherence across a spectrum of chronic conditions. METHODS: Item generation and domain structures were based on literature and expert opinion. Interviews with 33 patients with asthma, diabetes, and heart failure were used to develop 47 Likert-type items. These were tested on the Web with 605 patients with asthma, diabetes, and depression. Factor analysis was performed to identify conceptually similar item groupings; and item validity in relation to a self-reported measure of adherence, the distribution of item responses, and factor structure were studied to select final survey items. RESULTS: Twenty items were retained based on correlation with validity criteria and clinical relevance in the following domains: Lifestyle, Attitudes and Beliefs, Help from Others, Talking with Healthcare Team, and Difficulty Taking Medicines. A post hoc cut point dichotomizing responses into “present” and “absent” was selected for each item. The Barrier Total Index (BTI), the number of “barrier-present” items, had an observed range from 0 to 18, a mean of 4.2 (±3.4), and good reliability (Cronbach's alpha = 0.77). The validity of the BTI with a self-report of a missed dose of medicine in the past week was excellent. Patients who “missed” had a mean of 6 barriers vs. 2.6 for those who did not (p<0.0001). CONCLUSION: The ASK Adherence Barrier Survey appears to be a useful tool to identify barriers to adherence in chronic diseases. The survey can facilitate discussion of adherence and identify opportunities to implement barrier-specific interventions.