Background: Necrotizing Entero Colitis (NEC) and Focal Intestinal Perforation (FIP) affect almost exclusively preterm babies <1500 g and the incidence ranges up to 15% and gut perforation in NEC (NECp) strongly affects clinical outcome and mortality. Aiming to understand the mechanism underlying the disease prenatal and birth risk factors, pregnancy age, gender, birth weight, postnatal complications like PDA, or coagulation disorder and drug administration (antibiotics, indomethacin), mechanical ventilation or parenteral nutrition had to be considered to induce NEC, NECp or FIP. Methods: This is a retrospective, single-centre review including preterm newborn with NEC, NECp or FIP in a period of 10 years, including all preterm with diagnosed NEC, NECp and FIP born before the 37th Gestational Week (GW) and excluding children with NEC, NECp or FIP born after the 37th GW, as well as premature babies without NEC, NECp or FIP. All data were obtained through the analyses of maternal and NICU medical records. During the survey period 27.414 deliveries occurred in this centre, therewith 76 affected preterm were included in our cohort. Results: Premature mortality risk was significantly higher in male than in female with NEC and NECp (p=0.040). A coagulation disorder (p=0.018) as well as insulin substitution (p=0.008) were significantly more frequent in NECp and FIP. FIP preterm received significantly more antibiotics (p=0.009) and glucose (p=0.021) than NEC preterm. NECp preterm were more frequently administered surfactant (p=0.018), needed longer respiratory support (p=0.034), were more often intubated (p=0.022) and had longer additional oxygen supply (p=0.013) than NEC or FIP. FIP and NECp preterm received more often fresh frozen plasma (p=0.031) and were significantly longer parenteral fed (p=0.035). Minimizing preterm stress by implementation a standardized “minimal handling” protocol by nurses and doctors reduced significantly the number of NECp (p<0.001). Conclusion: Early detection and appropriate therapy for NEC, NECp or FIP particularly in early stages of disease help to reduce mortality. Stress decrease via a standardized “minimal handling” protocol could be practiced everywhere regardless of the geographical location and equipment of the neonatal intensive care unit.