Introduction. The COVID-19 pandemic has significantly impacted global health, with Eastern Europe experiencing notable excess morbidity and mortality and vaccine hesitancy. This study utilized the Behavior Integration (BI) framework to identify barriers and motivators for COVID-19 vaccination and develop strategies to increase vaccine demand and confidence in Moldova, North Macedonia, and Serbia. Methods. A mixed-methods approach was employed, including qualitative interviews and quantitative surveys. The BI framework was used to integrate human behaviors with technical and operational considerations throughout the project. Results. A total of 2742 online surveys were collected in Moldova and Serbia, revealing significant barriers such as vaccine safety concerns (OR = 1.839, 95% CI: 1.328–2.547 in urban Moldova; OR = 1.990, 95% CI: 1.351–2.931 in urban Serbia), logistical challenges, and lack of institutional trust. Conversely, motivators included personal health concerns, recommendations from health care providers, and the desire to travel. The proposed social and behavior change strategy included a continuing medical education course that trained 2403 medical providers, with post-test results showing a 99% improvement in knowledge and confidence in applying the information, and collective engagement workshops for 3260 chronic disease patients and 842 pregnant women, of which 7% were vaccinated against COVID-19. Conclusions. The BI approach effectively identified and addressed vaccination barriers and motivators, leading to tailored strategies that increased vaccine uptake. Continuous stakeholder engagement, adaptive learning processes, and local organizations are crucial for refining program implementation, ensuring sustainability, and promoting public health.
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