Myelodysplastic syndromes (MDS) are a group of hematological malignancies with poor survival. Although previous studies have identified the prognostic role of multiple demographic and clinical characteristics, the potential role of lifestyle factors has not been evaluated. In this study, we conducted an extensive assessment of the predictors of MDS survival, with a special focus on lifestyle factors. A total of 616 patients (median survival = 4.1 years) were included in the analysis, and multivariate Cox proportional hazard models were utilized to estimate hazard ratios. Compared with non-smokers, MDS patients who smoked at the initial clinical encounter had a significantly increased risk of death [hazard ratio (HR) = 1.46, 95% confidence intervals (CI): 1.07-2.00]. The elevated risk was restricted to men (HR = 1.76, 95% CI: 1.21-2.56) and not observed among women (HR = 0.98, 95% CI: 0.51-1.85). When patients were stratified by the IPSS categorization, a near three fold increased risk of death was associated with smoking among patients with low-risk MDS (HR = 2.83, 95% CI: 1.48-5.39), whereas smoking did not appear to influence the survival of patients with intermediate- or high-risk MDS. This study was the first to identify smoking as a significant and independent predictor of MDS survival, particularly among low-risk patients.