PURPOSE: Epirubicin is an antitumor drug, particularly used in the treatment of the breast cancer. The peripheral intravenous infusion of epirubicin frequently causes venous irritation such as, erythema, injection site pain, and phlebitis. The purpose of the present study was to investigate the risk factor associated with the epirubicin-induced venous irritation and to establish a suitable administration method of epirubicin. METHODS: The phlebitis scores (Visual Infusion Phlebitis score) were evaluated retrospectively using the collected nursing record. We analyzed the risk factor associated with venous irritation in 97 patients administered with epirubicin from December 2004 to September 2008. We subsequently changed the regimen of epirubicin and examined the incidence of venous irritation in 26 patients administered with epirubicin from August 2009 to March 2010. RESULTS: The phlebitis scores were significantly higher in the patients treated with ready-to-use solution compared with lyophilized powder (P = 0.04). Based on this result, we switched the formulation of epirubicin to lyophilized powder. After the intervention, the phlebitis scores were significantly decreased (P = 0.003). An ordinal logistic regression analysis revealed that use of ready-to-use solution was a significant predictor for venous irritation (odds ratio = 3.70; 95%, confidence intervals, 1.29-11.45; P = 0.02). CONCLUSIONS: The use of ready-to-use solution was a risk factor for epirubicin-induced venous irritation. The change of formulation by pharmacist intervention decreased the risk of venous irritation.