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To assess the risk for intraventricular hemorrhage (IVH) in very low birth weight preterm infants with patent ductus arteriosus (PDA) and low platelet count with treatment with cyclooxygenase (COX) inhibitors.Diagnosis and treatment of PDA, as well as risk factors for IVH, were assessed using prospectively collected data of all infants born at a gestational age <32 weeks and with a birth weight ≤1500 g at Innsbruck University Hospital (January 2003-December 2009). Infants with severe thrombocytopenia (<50 × 109/L) were excluded from analysis.Sixty-five (20%) of the 325 infants had IVH, and 149 (45.9%) of the 325 were treated with COX inhibitors. Treatment of PDA with COX inhibitors was not an independent risk predictor for IVH in preterm infants with platelets ≥100 × 109/L. However, COX inhibitors amplified the risk of bleeding in the presence of moderately decreased platelets (50-99 × 109/L) on days of life 2-7. Multivariable OR for IVH were 0.89 [95% CI 0.43-1.87] for patients with platelets ≥100 × 109/L and treatment with COX inhibitors, 3.40 [95% CI 1.13-10.29] for those with moderately decreased platelets without treatment, and 53.3 [95% CI 5.9-484] for patients with both moderately decreased platelets and COX inhibitor treatment compared with those with platelets ≥100 × 109/L and no treatment (reference group) (P < .001).In very low birth weight infants with moderate thrombocytopenia treatment with COX inhibitors increased the risk for intracerebral bleeding. Any benefits of this therapy should be carefully balanced against this potential hazard.