Some of the expected adverse drug reactions of the systemic triazole antifungals (fluconazole and itraconazole) can be attributed to drug-drug interactions. OBJECTIVES: To quantify the frequency of concurrent drug use that may cause drug-drug interactions (DDI) with triazole antifungals. METHODS: A retrospective observational study was conducted of adult patients who received systemic triazole treatment in 6 hospitals comprising the PHARMO Inpatient database during 1994 -2002. The list of triazole interacting drugs, the severity and effect of interaction was obtained from the Drug-Reax® system and the Drug Interaction Facts. Concomitant use of triazole interacting drugs was identified for each day of systemic triazole treatment. RESULTS: The study cohort comprised 1374 patients with a total of 1522 hospitalizations during which fluconazole (n=1329) or itraconazole (n=193) were prescribed. The majority of hospitalizations were for neoplasms (21.6%), respiratory (15.2%) and digestive disease (14.3%). The median duration of triazole treatment was eight days. Among patients receiving fluconazole, 55.3% were prescribed at least one interacting drug (>95% with potential for moderate or severe consequences) with 32.5% of patients receiving more than one interacting drug. The most frequently co-prescribed interacting drugs with fluconazole were haloperidol, digoxin, prednisolone, acencoumarol and theophylline. Among patients on itraconazole, 65.3% received at least 1 interacting co-prescription (74% moderate or severe), 41% received more than one interacting drug. The most frequently co-prescribed interacting drugs with itraconazole were ranitidine, acenocoumarol, prednisolone, pantoprazole and theophylline. The most frequent occurring effect of the DDI would be an increased concentration of the interacting drug (in 50% of hospitalizations), in 10% a serious toxicity could occur due to the DDI (QTc prolongation, rhabdomyolysis). CONCLUSIONS: We showed that the potential for moderate and severe drug-drug interactions is prominent in hospitalized persons who are treated with triazoles. These DDI's may impact on the outcomes of this patient population.