Background: Ethiopia is one of the countries with a significant shortage of medical blood. Patient caregivers can serve as an important pool of potential blood donors for many reasons. However, limited data are available on the willingness of patient caregivers to donate blood in Ethiopia. Therefore, this study assessed patient caregivers' willingness to donate blood and associated factors in northwest Ethiopia. Methods: An institution-based cross-sectional study was conducted among 342 patient caregivers at the University of Gondar Comprehensive Specialized Hospital. A systematic random sampling technique was used to select the study participants. Data were collected using a pretested and interviewer-administered questionnaire. Data were entered into EPI data version 4.6 and exported to SPSS version 25 for analysis. The level of significance in the last model was declared based on a p-value of <0.05. Results: Patients caregivers' willingness to donate blood was 78.1% (95% CI: 74, 82). Attending primary (AOR = 2.91; 95% CI: 1.13, 7.54) and secondary education (AOR = 2.95; 95% CI: 1.19, 7.28), favorable attitude towards blood donation (AOR = 4.94; 95% CI: 2.62, 9.28), adequate knowledge of blood donation (AOR = 2.49; 95% CI: 1.18, 5.22), and ever donated blood (AOR = 3.95; 95% CI: 1.13, 13.84) were identified as significantly associated with willingness to donate blood. Conclusion: In this study, more than three-quarters of patient caregivers were willing to donate blood. Community encouragement and continuous awareness and motivational speeches about the need for blood donations within the community and in medical facilities would have been important to motivate patient caregivers to donate blood.