Circulating microRNAs (miRNAs) are potential biomarkers for cancer. We examined plasma levels of 2 miRNAs, let-7a and miR-16, in 50 patients with myelodysplastic syndrome (MDS) and 76 healthy persons using quantitative real-time PCR. Circulating levels of both miRNAs were similar among healthy controls but were significantly lower in MDS patients (P = .001 and P < .001, respectively). The distributions of these 2 miRNA levels were bimodal in MDS patients, and these levels were significantly associated with their progression-free survival and overall survival (both P < .001 for let-7a; P < .001 and P = .001 for miR-16). This association persisted even after patients were stratified according to the International Prognostic Scoring System. Multivariate analysis revealed that let-7a level was a strong independent predictor for overall survival in this patient cohort. These findings suggest that let-7a and miR-16 plasma levels can serve as noninvasive prognostic markers in MDS patients.