Background. Prolonged rupture of membranes (PROM) is a common and significant cause of preterm labor and has a major impact on neonatal morbidity and mortality. The aim of this study was to determine maternal risk factors and the prevalence rate of neonatal complications following PROM . This study also detected the role of maternal antimicrobial treatment on neonatal complications.Methods: This cross-sectional study was performed at Ghaem hospital, Mashhad, Iran; from March 2008 to April 2010 to evaluate newborns’ outcome that were born from mothers with prolonged premature rupture of membranes (PROM> 18 hours). Maternal risk factors, antibiotic administration and its influences on neonatal complications were evaluated. Eligible infants were categorized into group I (symptomatic infants), II (mother with chorioamnionitis) and III (asymptomatic infants).Results. 150 infants were included in the study. 12 (7.7%) infants had definitive infections (meningitis, sepsis, pneumonia), 101(67%) infants were premature and 88(58.6%) infants had mothers with a history of antibiotic intake. Maternal risk factors were reported in the following order: previous PROM (10%), addiction (8%), high urinary tract infection (5/3%), diabetes (4.7%), placenta abruption (4.7%), preeclampsia (3/3%) and cercelage (2%). Neonatal complications related with PROM were prematurity (67.3%), respiratory distress syndrome (22.6%), asphyxia (8.6%), meningitis (5.2%), sepsis (4%), pneumonia (1.3%) and death (4.6%). History of antibiotic administration to mothers with PROM was negative in four babies with sepsis and one with meningitis.Conclusion. The most common complication of PROM was prematurity and its side effects, but infection is the most important modifiable complication. Although antimicrobial treatment of women with a history of PROM improves neonatal outcome through reducing neonatal sepsis and respiratory distress syndrome (RDS), but the incidence rate of meningitis and pneumonia may be increased.