Higher-risk myelodysplastic syndromes (MDS) are aggressive disorders with rapid progression to AML and short survival. Azacitidine has shown unprecedented survival advantage in these patients but its treatment schedule involves daily hospital administrations for 7 days every 4 weeks. Due to patient and staffing constraints, we have treated 50 patients with a 5-day dose-intensified (500 mg/m(2) total monthly dose divided in 5 days) azacitidine schedule in our center. The regimen was well tolerated, with Grade 3/4 adverse events seen in 24 % patients and only two discontinuations due to toxicity. The response rate was similar to that reported with the 7-day schedule: 16 % complete remissions, 32 % partial remissions, and 62 % transfusion independence. The median survival was 19.2 months from diagnosis. In addition, this regimen reduced hospital visits by 28 % and drug use by 30 %. Our results demonstrate the safety and efficacy of a dose-intensified 5-day regimen.