Clinical decision support systems (CDS) coupled with computerized physician/provider order entry (CPOE) can improve the quality of patient care and the efficiency of hospital operations. However, they can also produce unintended consequences. Using qualitative methods, a multidisciplinary team gathered and analyzed data about the unintended consequences of CPOE, identifying nine types, and found that CDS-generated unintended consequences appeared among all types. Further analysis of 47 CDS examples uncovered three themes related to CDS content: elimination or shifting of human roles; difficulty in keeping content current; and inappropriate content. Three additional themes related to CDS presentation were found: rigidity of the system; alert fatigue; and potential for errors. Management of CDS must include careful selection and maintenance of content and prudent decision making about human computer interaction opportunities.