Intraventricularhemorrhage (IVH) is one of thecommon morbidities among preterm neonates. In thepresentstudy, we set out to evaluate the efficacy of two prophylactic modalities (ibuprofen and indomethacin prophylaxis) for prevention of IVH in our local setting. A prospective study was carried out in Akbar-Abadi Hospital, Tehran-Iran (2013-2014). Ninety-six preterm neonates who cared in closed incubator entered the study. Neonates randomly assigned into 3 groups; control, oral indomethacin (0.2 mg/kg indomethacin daily for 3 days) and oral ibuprofen (10,5,5 mg/kg ibuprofen every 24 hours during 3) administration. For all subjects brain sonography examination was performed in 3rd day, first, 2nd week of life and when infants reached to 36 and 42 weeks of postmenstrual age. The IVH prevalence and the effectiveness of the drugs among groups were statistically assessed. Of all 93 subjects; 14 cases had IVH (15.1%). IVH was significantly more frequent in the controls than in other groups (P=0.049). Prophylactic treatment could significantly decrease the incidence of grade 3 or 4 IVH in experimental groups (P=0.008). There were no significant differences between the three experimental groups with respect to theincidence of GI bleeding, Oliguria, renal dysfunction or NEC (P>0.05). This study demonstrates that low-dose prophylactic indomethacin and ibuprofen are equally associated with a reduction of IVH without any significant side effects like renal dysfunction, GI bleeding or NEC.