We analyzed micro-RNAs (miRs) as possible diagnostic biomarkers for relevant comorbidities prior to and prognostic biomarkers for mortality following hematopoietic cell transplantation (HCT). A randomly selected group of patients (n = 36) were divided into low-risk (HCT-comorbidity index [HCT-CI] score of 0 and survived HCT) and high-risk (HCT-CI scores ≥ 4 and deceased after HCT) groups. There were 654 miRs tested and 19 met the pre-specified significance level of p < 0.1. In subsequent models, only eight miRs maintained statistical significance in regression models after adjusting for baseline demographic factors; miRs-374b and -454 were underexpressed, whereas miRs-142-3p, -191, -424, -590-3p, -29c, and -15b were overexpressed among high-risk patients relative to low-risk patients. Areas under the curve for these eight miRs ranged between 0.74 and 0.81, suggesting strong predictive capacity. Consideration of miRs may improve risk assessment of mortality and should be further explored in larger future prospective studies.