The under-representation of women in blood donation can lead to blood shortages. We aimed to determine the factors, which encourage or impede blood donations in women. The findings can help us in designing effective recruitment strategies that could encourage women to donate blood to cover the patients’ needs. This cross-sectional study was conducted in Shiraz, Iran, from the 1st of January 2017 to the 1st of August 2017 on women aged 18–60 years old. The demographic characteristics of the participants, the reasons that motivate blood donors and the factors that discourage non-donors were surveyed. Reasons for lapses in donors were also mentioned. The most frequent reasons for blood donation were altruistic causes (94.4%), moral and personal obligations (89.1%), the feeling of responsibility (82.7%), and awareness of the positive effects on their health (77.4%). The most common deterrents in non-donors were fear of developing anemia (68.4%) or weakness and dizziness (66%), unsuitability due to certain medical conditions (62.4%), and lack of a situation in which they were asked to donate blood (61.8%). Although altruistic reasons are the chief motivating factors for women to donate blood, the overall female contribution in blood donation remains low. Therefore, it is necessary to take measures aiming at informing women about the importance of blood donation and to reduce fears based on misinformation. Confidence in the blood donation organization must be a major consideration in future recruitment strategies to reassure women about the safety of blood donation.