Inter-organizational networks play an increasing role in delivering computer-mediated public services such as healthcare. Many networks govern through an infomediary (i.e., electronic broker) that brings together disparate member organizations. These networks can resemble an enterprise where standards and incentives for use are imposed on its partners. This study seeks to extend an enterprise IT governance (ITG) concept to the U.S. e-prescribing network as it transitions from a paper-based network to a computer-mediated one. The operating model, proposed by Ross et al (2006), emphasizes choices in standardization and integration to align strategy with operational processes to improve enterprise performance. Missing in their work is evidence that macro-level choices embedded in the operating model directly impact network workflow. A comparative synthesis traces the changes made to the U.S. e-prescribing operating model to their impact upon the roles and relationships among network members. Some workflow mis-alignments were traceable to the operating philosophy imposed by healthcare policy-makers. The study suggests IT alignment in networks may be better achieved through governing operating models rather than the traditional ITG focus on organizational forms.