Background With an increasing number of options for atrial fibrillation (AF) stroke prophylaxis, there are several medication-related factors to consider. This study aimed to gain a better understanding of which preference factors influence patient decisions when selecting AF stroke prophylaxis. Objective To determine the factors that influence patient stroke prophylaxis decisions and preferred therapeutic options. Methods A questionnaire about AF stroke prophylaxis medication options was distributed to participants at risk of AF. Preferences were elicited through ranking and rating medication preference factor statements, then selecting most and least preferred treatment options. Results Reduced stroke risk and lowest risk of an intracranial haemorrhage (ICH) had the highest median preference factor ranking of 2 (IQR, 1-3.5 for stroke reduction; 2-4 for ICH risk). Reducing stroke risk, availability of a lab test to assess drug effect, and availability of an antidote were the preference factors with the highest ratings. Apixaban was the most preferred treatment option (44% blinded to drug name, 37% unblinded) while 'No treatment' was the least preferred option (48% blinded, 52% unblinded). Conclusions Reducing stroke risk and limiting ICH risk were the most important medication factors to participants. High inter-participant preference variability suggests the importance of including the patient in decision-making when selecting AF stroke prophylaxis.