Purpose Evaluation of the effectiveness of the feeding protocol in improving feeding interruption (FI) and clinical outcome in critically ill patients. Materials and methods This was a single-center, retrospective, and prospective cohort study design evaluating the nutritional characteristics and adequacy, and the causes and clinical outcomes of FI, pre- and post-feeding protocol implementation. The risk factor for ICU mortality was also identified. Results In total, 430 patients were included, 217 in the pre-protocol group and 213 in the post-protocol group. After protocol implementation, energy and protein intake significantly improved, and the total target nutrition was achieved. The post-protocol group was prescribed a more energy-dense formula (29.0% vs. 55.4%, p < 0.001), a protein supplement (27.6% vs. 56.3%, p < 0.001), and a prokinetic agent (38.7% vs. 48.8%, p = 0.03). There was no difference in the duration of feeding interruption (28 h vs. 30 h, p = 0.60). Implementation of feeding protocol did not affect ICU mortality (OR 0.508, CI 0.250–1.032, p = 0.06). The mortality predictors were SOFA score, underweight, and illness-related FI episode. Conclusion Implementation of the feeding protocol improved feeding strategies and overall nutritional intake; however, it did not improve FI. Illness-related FI was associated with a reduction in survival of critically ill patients.