The COVID-19 pandemic has had a profound global impact, particularly on high-risk populations, such as those with underlying medical conditions. In response to the evolving pandemic landscape and the constant surge in the need to vaccinate among vulnerable cases in Taiwan, the Taiwan Association of Family Medicine (TAFM) has developed recommendations on COVID-19 vaccination for high-risk groups. Based on a comprehensive literature review and expert panel discussions, a total of 25 evidence-based recommendations have been developed to serve as a reference for vaccination strategies, highlighting the increased risk of severe COVID-19 outcomes among individuals with complications such as diabetes, obesity, chronic kidney disease, cardiovascular disease, and respiratory illnesses. The recommendations emphasize the safety and effectiveness of COVID-19 vaccines, particularly mRNA vaccines, for the aforementioned high-risk populations and underscore the critical roles of family physicians in response to severe COVID-19 outcomes, including routine screening, health education, vaccine administration, and continuous research to optimize strategies. The TAFM recommendations provide a robust, evidence-based framework that meets clinical practice requirements and provides effective guidelines for physicians, healthcare institutions, and governments in tailoring vaccination efforts to address the unique needs of high-risk groups in Taiwan. Ongoing monitoring and proactive vaccination drives are essential for ensuring the effectiveness of these recommendations in the evolving COVID-19 landscape, while also accentuating the continuous efforts of family physicians in preventing endemic diseases.