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Introduction. Therapy of high risk myelodysplastic syndromes (MDS) remains unsatisfactory. The only treatment that alters the natural history of the disease is allogeneic stem-cell transplantation, which can be offered to a limited number of young patients. Modern therapy predominantly focuses on prolonging survival, postponing potential acute myeloid leukaemia (AML) transformation and improving quality of life (QoL). New epigenetic therapy, especially methyltransferase inhibitors, has achieved these goals. Here, we present the experience of the Czech MDS Cooperative Group with 5-azacitidine treatment of patients with intermediate II and high risk MDS patients (IPSS), chronic myelomonocytic leukaemia II (CMML II) and AML with less than 30% myeloblasts in the bone marrow. Patients and results. Between October 2008 and June 2012, we used azacitidine treatment in 111 patients (66 M, 45 F), median age 68 years (range 48-85) with the diagnosis: 44 RAEB II, 13 RAEB I, 9 CMML II, 6 RCMD, 28 AML < 30% MB, 7 AML > 30% MB and 4 MDS/MPS. Median follow-up was 8.8 month (range 1-32), median number of cycles of azacitidine was 5 (range 1-28). The most common adverse events included haematological toxicity with neutropenia grade (Gr) 3/4 in 54.9% and thrombocytopenia Gr 3/4 in 70.3%. Non-haematological side effects, mostly only Gr1/2, were gastrointestinal in 21.6% and local reactions and fatigue in 31.5%. Response. The overall response rate (ORR) was 42.4% (CR 19.6%, CRi 6.5%, PR 16.3%), stable disease (SD) was achieved in 19.6% and haematological improvement (HI) in 57.4%. After one year, based on Kaplan-Meier estimates, 67.8% of patients were alive and the median overall survival (OS) was 16.4 months. We also analysed several clinical parameters collected at the start of azacitidine treatment as prognostic factors for OS (age, sex, ECOG performance status (PS), transfusion dependency, peripheral blast percentage, neutrophil count, platelet count, bone marrow blast percentage, fibrosis, percentage of erythroid precursors in bone marrow, cytogenetic data, WHO classification, IPSS, primary and secondary aetiology of MDS). Conclusion. Our results correlate very well with other published data (AZA 001, CALGB 9221). OS data are comparable with other "real life" studies. It is also important to take into consideration that our group also included very high risk patients (relapsed, refractory to previous treatment, post-transplant patients and AML with more than 30% myeloblasts). Nevertheless, our results are very promising and support the positive effect of azacitidine compared to standard therapy in high risk MDS patients. The analysis performed so far shows that from the aspect of OS, best response correlates with: cytogenetic aberration, peripheral blast count, neutrophil count and ECOG PS. [ABSTRACT FROM AUTHOR]