Introduction/Objective. The increased presence of lipid particles in blood is one of most common reasons that transfusion units are unusable. The risk factors for lipemic plasma in donated blood are not completely known. The aim of this study is to identify the factors that influence plasma to be fatty so that we can prevent further storage costs and eliminate unusable transfusion units. Methods. This case?control study was conducted in 2017, and 1552 respondents were included in the study. The control group included 1502 subjects whose blood was not lipemic, while 50 patients with lipemic blood were selected for the case group. The presence of lipemic blood was assessed by inspection, while data were collected by clinical laboratory tests and a questionnaire. Results. Our findings show that multiple blood donors with lipemic blood were significantly older (p < 0.0005) and have higher systolic and diastolic pressure (p < 0.0005), high triglyceride levels (p < 0.0005), and lower levels of hemoglobin (p < 0.0005). Additionally, the presence of lipemic plasma was associated with female sex (p = 0.002), blood type (p = 0.016), heart disease (p < 0.0005), smoking (p < 0.005), diabetes (p = 0.001), lipid intake prior to blood donation (p < 0.005) and venipuncture therapy (p < 0.0005). Systolic pressure is a reliable predictor of lipemic blood (AUROC = 0.901, p < 0.0005). Conclusion. Our study provided a rational explanation and identified some of the risk factors that may help identify potential donors with lipemic blood.