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To describe the establishment of a fungal chemoprophylaxis protocol in very low birth weight infants (VLBW). To asses safety, tolerability, and effectiveness of fluconazole administration to these patients.According to published scientific evidence (search on MEDLINE 1994–2001) inclusion criteria for the protocol were defined: gestational age <28 weeks and birth weight <1500 g. Fluconazole was given intravenously by infusion. A pharmacotherapeutic follow-up of patients included on the protocol was performed for 1 year.Sixteen patients were included on the protocol, two of them died because of causes not related to the drugs given. Significant drug interactions were not observed. Fluconazole side effects were not reported either. None of the patients who finished the chemoprophylaxis showed signs or symptoms of fungal infection.Fluconazole chemoprophylaxis in this small number of patients has shown an excellent safety and tolerability profile. The lack of fungal infection points out the possibility of using fluconazole to reduce morbidity and mortality in VLBW.