Background The Neonatal Multiple Organ Dysfunction (NEO-MOD) scoring system is used to predict mortality in infants with multiple organ dysfunction syndrome (MODS). The NEOMOD scoring system was extended to include involvement of the microvascular system. This modified scoring system was developed to enable more accurate and earlier diagnosis of MODS in premature infants. Objective To evaluate the modified NEOMOD scoring system in preterm infants with MODS and compare its effectiveness with the NEOMOD scoring system. Methods This prospective study was performed in a tertiary neonatal intensive care unit. A total of 198 premature infants were enrolled. Infants were evaluated for development of MODS by using the modified NEOMOD scoring system until discharge or death according to clinical and laboratory findings. Infants who had organ dysfunction in 2 or more organ systems had MODS diagnosed. Results In the 160 infants (80.8%) with MODS, the gastrointestinal system, respiratory system, and hematologic system were involved most often. The gastrointestinal system, respiratory system, and acid-base metabolism were involved initially in 99.4%, 86.3%, and 26.3% of infants, respectively. The mean modified NEOMOD score for the infants who died in the first 28 days after birth was significantly higher than the mean score for infants who survived. The number of systems involved was also higher in infants who died. Conclusions The modified NEOMOD scoring system is a safe and accurate tool for determining both mortality rate and dysfunction of multiple organ systems affecting mortality in preterm infants.