In the past three years, evidence based medicine emerged as a powerful force in an effort to improve quality and health outcomes, and to reduce cost of care. Computerized physician order entry (CPOE) applications brought safety and efficiency features to clinical settings, including ease of ordering medications via pre-defined sets. Order sets offer promise of standardized care beyond convenience features through evidence-based practices built upon a growing and powerful knowledge of clinical professionals to achieve potentially more consistent health outcomes with patients and to reduce frequency of medical errors, adverse drug effects, and unintended side effects during treatment. While order sets existed in paper form prior to the introduction of CPOE, their true potential was only unleashed with support of clinical informatics, at those healthcare facilities that installed CPOE systems and reap rewards of standardized care. Despite ongoing utilization of order sets at facilities that implemented CPOE, there is a lack of quantitative evidence behind their benefits. Comprehensive research into their impact requires a history of electronic medical records necessary to produce large population samples to achieve statistically significant results. The study, conducted at a large Midwest healthcare system consisting of several community and academic hospitals, was aimed at quantitatively analyzing benefits of the order sets applied to prevent venous thromboembolism (VTE) and treat pneumonia, congestive heart failure (CHF), and acute myocardial infarction (AMI) - testing hospital mortality, readmission, complications, and length of stay (LOS) as health outcomes. Results indicated reduction of acute VTE rates among non-surgical patients in the experimental group, while LOS and complications benefits were inconclusive. Pneumonia patients in the experimental group had lower mortality, readmissions, LOS, and complications rates. CHF patients benefited from order sets in terms of mortality and LOS, while there was no sufficient data to display results for readmissions and complications. Utilization of AMI order sets was insufficient to produce statistically significant results. Results will (1) empower health providers with evidence to justify implementation of order sets due to their effectiveness in driving improvements in health outcomes and efficiency of care and (2) provide researchers with new ideas to conduct health outcomes research.