Clinical care guidelines optimize patient care, including Enhanced Recovery after Surgery (ERAS®) guidelines specific to surgery. However, despite their efficacy, compliance to guidelines by providers remains a challenge. Understanding ways to predict, and thus prevent, non-compliance can aid in not only improving uptake by providers but improving post-surgical recovery for patients. Four approaches were taken to understand and assess these issues. A novel method was developed, coined Vertical Compliance, for measure ERAS compliance with the aim to predict and prevent adverse surgical outcomes before they occur by modifying compliance in real-time. Next, a multi-institutional, multi-surgical specialty retrospective data analysis revealed specific ERAS recommendations that - if not performed - predicted adverse patient outcomes such as increased length of stay (LOS) and clinically-relevant complications. However, understanding barriers to compliance in the first place can potentially improve their uptake via targeted mitigation strategies. A meta-analysis was conducted for the overall medical literature and regression models developed to understand which barriers predict non-compliance to guidelines. Finally, to understand barriers to compliance specific to surgery and ERAS, a survey was developed and analyzed using a mixed-methods approach to understand which barriers to compliance predicted reduces feelings of compliance assurance amongst ERAS professionals. While conceptually different, vertical compliance and the multi-institutional data analysis revealed similarities in which specific recommendations predict adverse outcomes, including oral carbohydrate loading, early removal of Foley catheter, and limited use of nasogastric tubes. The two studies examining barriers to compliance found concordance in which barriers most impact compliance, specifically presence of external barriers and familiarity with the guidelines. In the ERAS-specific barriers study, lack of motivation and agreement were also found to drive compliance. Taken both individually and collectively, these four studies reveal why predicting adverse surgical outcomes due to non-compliance to evidence-based care is important, yet, predicting barriers may prove a critical element to preventing that non-compliance before it occurs.