We performed a retrospective study to predict the risk factors related to general discomfort, limitations in activities of daily living (ADLs), and intention of a second donation in hematopoietic stem cell (HSC) donation. The subjects of this study were 1,868 consecutive unrelated volunteer donors who donated HSCs through the Korea Marrow Donor Program between November 2007 and April 2014. Bone marrow (BM) collections were performed without administration of granulocyte-colony stimulating factor (G-CSF) and peripheral blood stem cell (PBSC) collections were performed after mobilization with G-CSF administered subcutaneously for 4 or 5 consecutive days at a daily dose of around 10 mcg/kg of body weight. General discomfort and limitations in ADLs were assessed by numerical measurement (scores of 0 to 10), and donor’s intention of a second donation by yes or no reply. The post-donation questionnaires were completed within 48 hours after HSC collection, and at 1 week, 4 weeks, and 4 months thereafter. Pre-donation and post-donation predictors of general discomfort and limitations in ADLs were identified using univariate and multivariate linear regression considering donor demographic and clinical characteristics (age, sex, collection method, collection period) and the intention of a second donation on day 1. Pre-donation and post-donation predictors of the intention of a second donation were identified using univariate and multivariate logistic regression considering donor demographic and clinical characteristics (age, sex, collection method, collection period). Men represented 76.77% of donors. The median age at donation was 28 years (range, 19-51), and about 93.00% of donors were younger than 40 years of age. Among HSC collection, 61.88% were completed in a day. PBSC and BM collections accounted for 94.49% and 5.51% of HSC collections, respectively. Predictors of general discomfort included female sex (P< 0.0001), BM collection (P< 0.0001) or PBSC collection through a central line (P= 0.0349), 2-day collection (P= 0.0150), and negative or undetermined intention of a second donation on day 1 (P< 0.0001). Predictors of limitations in ADLs included age group of 30-39 years (P= 0.0046), female sex (P< 0.0001), BM collection (P< 0.0001) or PBSC collection through a central line (P< 0.0001), and negative or undetermined intention of a second donation on day 1 (P< 0.0001). The only predictor of positive intention of a second donation was male sex (P= 0.0007). Age, sex, collection method and period, and intention of a second donation should be considered risk factors when unrelated HSC donation is performed. As a collection method, PBSC collection through a peripheral line is recommended to alleviate physical stress and to improve ADLs. Female donors are more sensitive to HSC collection than male donors, and male sex of the donor is predictive of positive intention of a second donation. DisclosuresNo relevant conflicts of interest to declare.