BACKGROUND Blood donor recruitment remains an important worldwide challenge due to changes in population demographics and shifts in the demand for blood. Various cognitive models help predict donation intention, although the importance of affective deterrents has become increasingly evident. This study aimed to identify fears that predict donation intention, to explore their relative importance, and to determine if self-efficacy and attitude mediate this relationship, thus providing possible targets for intervention. STUDY DESIGN AND METHODS A total of 347 individuals (269 nondonors and 78 donors) living in Quebec responded to questionnaires assessing medical fears, psychosocial factors related to donation intention including the Theory of Planned Behavior (TPB) constructs, anticipated regret, and facilitating factors (i.e., time commitment and rewards). To examine the relative importance of these factors in the context of blood donation, the same questions were also asked about other medical activities that involve salient needle stimuli: flu vaccinations and dental examinations. RESULTS Medical fears, especially blood-related fears, were significantly associated with donation intention. Bootstrapping tests confirmed that this relation was mediated by attitude and self-efficacy. Underlining the importance of medical fears in the blood donation context, these fears were not associated with attitudes and intentions for dental examinations or flu vaccinations. CONCLUSION These results suggest that medical fears, especially blood-related fears, play a key role in predicting donation attitudes and intentions. Mediational pathways provide support for interventions to improve donation intentions by addressing specific fears while also improving a donor's belief in his or her ability to manage donation-related fears.