Little research has been conducted on the quality, benefits, costs, and financial considerations associated with health information technology (HIT), particularly informatics technologies such as e-prescribing, from the perspective of all of its stakeholders. To (a) identify the stakeholders involved in e-prescribing and (b) identify and rank order the positives and negatives of e-prescribing from the perspective of stakeholders in order to create a framework for payers, integrated delivery systems, policymakers and legislators, and those who influence public policy to assist them in the development of incentives and payment mechanisms that result in the better management of care. The Delphi method was used to enlist a panel of experts in e-prescribing, informatics, and/or HIT who have published in the field. This panel was presented with the results of initial research and an online survey of questions that sought to prioritize the quality, benefit, cost, and financial effects of e-prescribing from the perspective of each stakeholder. Eleven experts completed the first survey, which contained a list of stakeholders and positives and negatives associated with e-prescribing. Nine of the 11 experts completed the second survey, and 7 experts completed the final survey. From the results of these 3 surveys, a framework was presented to 5 framework experts, who were representatives from payers, integrated delivery systems, policymakers and legislators, and those who influence public policy. These framework experts were interviewed regarding the usefulness of the framework from their perspectives. The experts added stakeholders and many positives and negatives to the initial list and rank ordered the positives and negatives of e-prescribing from the perspective of each stakeholder. The aggregate results were summarized by stakeholder category. The positives and negatives were categorized as health, finance, effort, time, management, or data concerns. The framework experts evaluated the framework and found it useful. Positives and negatives associated with e-prescribing in the areas of quality, benefits, costs, and financial considerations can be rank ordered from the perspective of each stakeholder. The experts agreed on some points but disagreed on others. For example, they agreed that the main negative of e-prescribing from the perspective of pharmacists and pharmacies was its implementation costs but differed on the importance of providing faster information transfer. A framework was created that could be successfully used by payers, integrated delivery systems, policymakers and legislators, and those who influence public policy for the development of incentives and payment mechanisms. This research was supported by the National Library of Medicine of the National Institutes of Health under Award Number T15LM007088. The authors declare no conflicts of interest in the research. Study concept and design were contributed by DeMuro, Ash, Middleton, and Fletcher. DeMuro took the lead in data collection, along with Ash, and data interpretation was performed by DeMuro, Ash, Madison, Middleton, and Fletcher. The manuscript was written primarily by DeMuro, along with Ash and Middleton, and revised by DeMuro, Madison, and Ash, along with Middleton and Fletcher.