INTRODUCTION: Feeding critically ill patients on mechanical ventilation through a gastric tube can be challenging. Parenteral nutrition is often preferred when enteral feeding is problematic. Transpyloric feeding has been identified as an optimal method of nutrition for seriously ill premature infants. OBJECTIVE: This study aims to evaluate the advantages of transpyloric feeding combined with artificial ventilation compared to gastric feeding in premature neonatal patients. MATERIALS AND METHODS: The study included 64 patients with low tolerance to enteral feeding who required mechanical ventilation. The gestational age of the patients did not exceed 34 (32–35) weeks. Enteral feeding using a NAN® mixture was administered through a feeding tube placed outside the pylorus with an anti-reflux mechanism. The volume of enteral feeding was determined based on the requirement of 120 kcal/kg/day. RESULTS: The results of the study demonstrated that the group receiving transpyloric feeding had a significantly shorter hospital stay of 54 (41–67) days compared to the group receiving gastric feeding with 86 (64–94) days, p < 0.05. The weight gain in the group receiving gastric feeding was significantly lower at 89 (55–200) g compared to the group receiving transpyloric feeding with 161.5 (110–218) g. Similar findings were observed regarding a decrease in total protein levels on the 10th day of the study in the gastric feeding group with 36.5 (32–40) g/l compared to the transpyloric feeding group with 47 (42–50) g/l, p < 0.05. CONCLUSION: Transpyloric nutrition in premature infants on mechanical ventilation is a more efficient method compared to gastric feeding. The findings suggest positive effects including reduced hospitalization duration, prevention of hypoproteinemia, and significant increase in body weight.