© 2018 Academy of Nutrition and Dietetics Background Unintentional underfeeding is common in patients receiving enteral nutrition (EN), and is associated with increased risk of malnutrition complications. Protocols for EN in critically ill patients have been shown to enhance adequacy, resulting in better clinical outcomes; however, outside of intensive care unit (ICU) settings, the influence of a protocol for EN is unknown. Objective To evaluate the efficacy and safety of implementing an EN protocol in a noncritical setting. Design Randomized controlled clinical trial. Participants and settings This trial was conducted from 2014 to 2016 in 90 adult hospitalized patients (non-ICU) receiving exclusively EN. Patients with carcinomatosis, ICU admission, or <72 hours of EN were excluded. Intervention The intervention group received EN according to a protocol, whereas the control group was fed according to standard practice. Main outcome measures The proportion of patients receiving ≥80% of their caloric target at Day 4 after EN initiation. Statistical analyses performed Student t test or Wilcoxon rank-sum test were used for continuous variables and the difference between the groups in the time to receipt of the optimal amount of nutrition was analyzed using Kaplan-Meier curves. Results Forty-five patients were randomized to each group. At Day 4 after EN initiation, 61% of patients in the intervention arm had achieved the primary end point compared with 23% in the control group (P=0.001). In malnourished patients, 63% achieved the primary end point in the intervention group compared with 16% in the control group (P=0.003). The cumulative deficit on Day 4 was lower in the intervention arm compared with the control arm: 2,507 kcal (interquartile range [IQR]=1,262 to 2,908 kcal) vs 3,844 kcal (IQR=2,620 to 4,808 kcal) (P<0.001) and 116 g (IQR=69 to 151 g) vs 191 g (IQR=147 to 244 g) protein (P<0.001), respectively. The rates of gastrointestinal complications were not significantly different between groups. Conclusions Implementation of an EN protocol outside the ICU significantly improved the delivery of calories and protein when compared with current standard practice without increasing gastrointestinal complications.