Nasal carriage of MRSA is a significant risk-factor for the endogenous MRSA infection in immunocompromised patients. MRSA infection in ICU patients is thus mostly endogenous infection. To evaluate the impact of mupirocin use on the incidence of endogenous infection caused by MRSA in an intensive care unit, we prospectively treated all patients in the unit with mupirocin, 3 times daily for 3 days. This routine use of mupirocin led to eradication of nasal MRSA carriage in 81.8% of surveillance cultures and to a significant reduction in the total incidence of MRSA infection among MRSA carrier patients (0 episode in 11 patients) when compared to historical controls prior to the use of mupirocin (3 episodes in 7 patients). Mupirocin nasal ointment was significantly effective to prevent endogenous MRSA infection.