Background: One of the serious challenges facing neonatal medicine is meconium aspiration syndrome, delays in the treatment of which can lead to high mortality. Objectives: This study was designed and conducted with the aim of determining the mortality rate and risk factors affecting this rate in newborn infants with meconium aspiration syndrome. Methods: This study was conducted as a retrospective descriptive research on newborn infants with meconium aspiration syndrome hospitalized at the neonatal intensive care unit (NICU) of Fatemieh and Be'sat hospitals in Hamadan city during a 10-year period from 2004 to 2014. Demographic information of the mother and the newborn, hospitalization course, the need for mechanical ventilation, and complications and outcomes of disease were extracted and were analyzed using the SPSS software version 22. Results: Sixty-three newborn infants, diagnosed with meconium aspiration syndrome, were entered in this study, 40% of them were male, 85.7% wighed more than 2500 g, and 17.5% were post term, 25.3% had a five-minute Apgar Score (AS5min) of less than seven, 39.6% were nonvigorous at birth, 31.8% needed to be placed on mechanical ventilation, and 14.3% died during the hospitalization course. There was a significant relationship between the need for mechanical ventilation, nonvigorous state at the birth, complications of disease and mortality rate. Conclusions: Despite the progress made in medicine, meconium aspiration syndrome is still one of the causes of newborn infants' mortality. The mortality and morbidity rates can be reduced by improvement in perinatal care, prevention of post term delivery, timely caesarean and effective neonatal resuscitation at birth.