The WHO recently proposed a new classification of myelodysplastic syndromes (MDS) based on uni- or multi-lineage hematopoietic involvement, blast count and cytogenetic features. The aims of this study were to evaluate the prognostic value of the WHO classification, to assess the role of known prognostic factors in MDS within these WHO subgroups, and to estimate mortality rates and life expectancy of the patients in the subgroups. Four hundred and ninety-one consecutive patients with a diagnosis of MDS made at the IRCCS Policlinico San Matteo, University of Pavia Medical School, Italy, between 1992 and 2002 were retrospectively evaluated and reclassified according to the WHO criteria. Cox proportional hazards regression was used to identify the most significant prognostic factors. A standardized mortality ratio (SMR) was calculated to compare the mortality of MDS patients with that of the general population. Overall survival (OS) and leukemia-free survival (LFS) differed significantly between RA and RCMD (P<.001 and P=.01, respectively), but not between RA and MDS with del(5q), or between MDS with or without ringed sideroblasts. There was a significant difference in LFS between RCMD and RAEB-1 (P=.006), and in both OS and LFS between RAEB-1 and -2 (P<.001). Overall, age and gender had significant effects on survival (P<.001), older age and male gender negatively affecting the prognosis. These effects were statistically significant for RA and RCMD patients (P values from.01 to <.001), but not for those with RAEB. The mortality rate of all patients with RA/RARS aged 70 years or older and the male subgroup aged 65-70 years old did not differ from that of the general population. Cox regression analysis with time dependent covariates was applied to evaluate the prognostic value of needing transfusion. Patients with RA/RARS who became transfusion-dependent had a significantly shorter life expectancy than those who did not (P=.01) except for patients aged 70 years or older whose life expectancy was only marginally shorter than that of the general population (SMR=1.90, P=.03). Cox regression showed that IPSS significantly stratified OS and LFS of WHO subgroups (P=.005 and P=.003, respectively). Among IPSS variables, blast count and peripheral cytopenia failed to predict survival within the WHO subgroups, while karyotypic abnormalities, classified according to IPSS, significantly affected OS and LFS of MDS stratified in WHO categories (P=.03 and P=.02, respectively). In conclusion, the new WHO classification of MDS has relevant prognostic value. Cytogenetics is the only independent prognostic factor significantly affecting survival of patients classified into these WHO subgroups. MDS with uni-lineage dysplasia identifies a subset of truly low risk patients, whose survival is significantly affected by demographic characteristics. Patients with refractory anemia who are older than 70 years, as well the males aged between 65 and 70 years, have a life expectancy similar to that of the general population, and only slightly worsened by becoming transfusion-dependent. According to these results, extending curative approaches, such as non-myeloablative transplantation, to these groups of patients does not seem advisable.