The myelodysplastic syndromes (MDS) are a collection of hematologic disorders that affect older adults, and whose baseline characteristics and risk factors for evolution to acute myeloid leukemia (AML) and death have not been completely defined. We analyzed a large unselected cohort of 214 patients with MDS from the University of Pittsburgh Network Cancer Registry in Western Pennsylvania. Patients’ follow-up was 22 months, at the end of which 72.9% of patients were dead. Overall, the 36-month survival rate was 19.0% (95% CI: 14.0–24.5%); 22.4% (95% CI: 16.4–29.0%) for patients with lower-risk MDS; and 5.0% (95% CI: 0.1–14.8%) for patients with higher-risk MDS (p ¼ 0.0007). During follow-up, 32.9% of the patients developed AML. Family history of cancer and having 􀀁5% blasts at diagnosis were statistically significant predictors for progression to AML. A higher risk of death also was associated with age 470 years and previous diagnosis of another cancer. More than three cycles of chemotherapy sessions and a platelet count of 􀀁50 6 103/mm3 were inversely associated with death. This study suggests the need to incorporate laboratory results such as percentage blasts and platelet counts as well as epidemiologic data on family history of cancer in future outcome studies on MDS.