We retrospectively analyzed the results of hypomethylating therapy in 586 patients (azacitidine in 423 and decitabine in 163) with International Prognostic Scoring System (IPSS) lower-risk myelodysplastic syndrome (MDS). The patients were reclassified with newer scoring systems (revised IPSS [R-IPSS], revised WHO classification-based Prognostic Scoring System [R-WPSS], and Lower Risk Prognostic Scoring System [LR-PSS]), and 21.8-38.4% of patients had high or very high risk features by the newer scoring systems. Median overall survival (OS) was 27.3 months and newer scoring systems well stratified the patients in terms of OS (R-IPSS, P=0.001; R-WPSS, P<0.001; LR-PSS, P<0.001). Hematologic improvement (HI) was observed in 279 patients (47.6%). OS differed by the achievement of HI (39.4% vs. 36.2%, P=0.067). The differences were significant only in patients of intermediate or high risk group by LR-PSS (P=0.034) or R-IPSS (P=0.018). In summary, IPSS lower-risk MDS included a broad range of prognosis, and hypomethylating therapy induced HI in approximately half of the patients. Achievement of HI was associated with longer survival, especially in patients with intermediate or high risk features by newer scoring systems. Hypomethylating therapy seems to have potential benefits in IPSS lower-risk MDS.