Objectives: To compare the effect of hypocaloric versus standard enteral feeding on clinical outcomes in critically ill adults, and to investigate the influence of protein intake upon the outcome effects of hypocaloric feeding., Design: A meta-analysis of randomized controlled trials (RCTs) and trial sequential analysis (TSA) were carried out., Setting: Intensive Care Unit (ICU)., Patients: Or participants Critically ill adults., Interventions: Hypocaloric enteral feeding versus standard enteral feeding., Main Variables of Interest: The primary outcomes were all-cause short-term mortality and the incidence of nosocomial infection., Results: Eleven RCTs met the inclusion criteria; of these trials, two were judged as having low risk of bias. Compared with standard enteral feeding, hypocaloric enteral feeding had no benefits in terms of reducing short-term mortality, the incidence of nosocomial infection, or long-term mortality, though it had a positive impact upon the incidence of gastrointestinal intolerance. The TSA further confirmed these results. In turn, hypocaloric enteral feeding had no effects upon the incidence of bloodstream infection, pneumonia, hypoglycemia or the duration of mechanical ventilation, ICU stay, or in-hospital stay. The above results remained unchanged in the sub-analysis of trials with a low risk of bias, trials administering a similar dose of protein, or trials administering different doses of protein., Conclusions: Compared with standard enteral feeding, hypocaloric enteral feeding was not associated with better clinical outcomes in critically ill adults, except for a lower risk of gastrointestinal intolerance. The difference in protein intake between groups might have no influence on the outcome effects of hypocaloric enteral feeding. High quality randomized controlled trials are needed to confirm this, however., (Copyright © 2019 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)