Introduction: Transfusion of blood products, especially red blood cells (RBC) is the most common medical intervention administered in North-American hospitals. The indications for transfusion are diverse but they largely aim at increasing oxygen delivery to tissues to improve patient clinical outcomes. Transfusion can also have deleterious effects. In fact, there is evidence that RBC transfusion may be ineffective, or even harmful in some populations where its use should in theory be beneficial. Seeking explanations for the beneficial and deleterious effects of red blood cell transfusions is necessary. The primary objective of this research is to investigate the associations between donor characteristics and RBC transfusion recipient outcomes. Methods: My thesis consists of a systematic review and meta-analysis of the literature regarding the association between blood donor characteristics and outcomes of the recipient, and the development of a framework linking the donor-recipient continuum using data collected from blood donors by Canadian Blood Services and clinical outcome data from large hospital and provincial clinical-administrative databases. Based on the framework, an epidemiological analysis was conducted to assess the effect of donor sex, age and ABO-Rh mismatch on RBC recipient outcomes. Results: Our systematic review found 58 studies evaluating 17 different donor characteristics. Five studies evaluated donor age as a risk factor for RBC transfusion outcome and 17 studies evaluated donor sex. We successfully developed an analytical framework allowing for a robust analysis of the impact of donor characteristics on RBC recipient outcomes that included 30,503 RBC recipients, 80,755 blood donors and a total of 187,960 transfusion episodes. We found that young age and female sex are donor characteristics significantly associated with adverse outcomes after RBC transfusion. Our newly developed framework, as well as our epidemiological findings, have the potential to influence future research in transfusion medicine and transfusion practices.