Intraventricular hemorrhage (IVH) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants; 80-90% of cases occur between birth and the third day of life. In a retrospective case control clinical study, files of all premature infants with birth weights <1500 grams admitted between April 2004 and October 2005 to the Neonatal Intensive Care Unit (NICU) of Akbar Abadi Hospital were reviewed. We determined risk factors that predispose to the development of high-grade IVH (grades 3 and 4) in VLBW infants. Thirty-nine infants with IVH grade 3 and 4 were identified. A control group of 82 VLBW infants were also selected. Prenatal data, delivery characteristics, neonatal course data and reports of cranial ultrasonography were carefully collected for both groups. Those variables that achieved significance (p<0.05) in univariate analysis were entered into multivariate logistic regression analysis. A total of 325 VLBW infants were evaluated. Mortality rate was 21.5%. Multivariate logistic analysis showed that the following factors are associated with greater risk of high-grade IVH occurrence: lower gestational age (OR: 3.72; 95% CI: 1.65-8.38), birth weight (OR: 3.42; 95% CI: 1.65-8.38), mechanical ventilation (OR: 4.14; 95% CI: 1.35-12.2), tocolytic therapy with magnesium sulfate (OR: 4.40; 95% CI: 1.10-24.5), hyaline membrane disease (HMD, OR: 3.16; 95% CI: 1.42-7.45), symptomatic hypotension (OR: 2.32; 95% CI: 1.06-5.42), hypercapnia (OR: 1.9; 95% CI: 1.1-3.4) and Apgar score at 5 minutes (OR: 1.58; 95% CI: 1.59-6.32).