OBJECTIVE To develop and initially validate a questionnaire designed to assess barriers to self-management perceived by persons with multiple chronic medical conditions. We hypothesized that persons who reported increased barriers to self-management would also report lower general health status and a greater disease burden. METHODS A cross-sectional survey was done of Health Maintenance Organization members aged 65 years or older with varying numbers of chronic medical conditions. On the basis of a previous qualitative investigation, we have identified 13 domains representing potential barriers to self-management. We developed questions to assess each of these domains and, for each, calculated coefficients alpha and assessed correlation of that domain with self-reported general health status and disease burden. RESULTS Respondents reported an average of 5.9 chronic conditions. Eight domains demonstrated acceptable internal consistency in this population. Nine of 13 domains correlated significantly in the expected direction with health status and/or disease burden. DISCUSSION These results provide an encouraging first step in developing a tool that will be clinically useful in assessing and addressing barriers to medical self-management for persons with co-morbidities. Use of assessments such as this in clinical settings may facilitate appropriate and efficient care management and improved health outcomes for this growing and vulnerable patient population.