Clinical decision support interventions are typically heterogeneous in nature, making it difficult to identify why some interventions succeed while others do not. One approach to identify factors important to the success of health information systems is the use of meta-regression techniques, in which potential explanatory factors are correlated with the outcome of interest. This approach, however, can result in misleading conclusions due to several issues. In this manuscript, we present a cautionary case study in the context of clinical decision support systems to illustrate the limitations of this type of analysis. We then discuss implications and recommendations for future work aimed at identifying success factors of medical informatics interventions. In particular, we identify the need for head-to-head trials in which the importance of system features is directly evaluated in a prospective manner.