PURPOSE: There is increasing interest in the understanding of key influences over successful implementation of health policies within ever-changing contexts of national health systems. The epidemiological transition in Vietnam, combined with an urgent need for improving efficiency of the national health system under the government's administrative reforms, form important facilitators of restructuring the public health system. This paper explored the implementation processes of policy on establishment of the Centers for Diseases Control (CDC) in Vietnam during 2016-2019. METHODS: The study employed a cross-sectional and mixed methods design. Staff surveys were collected at 55 out of 63 provinces and in-depth interviews, focus groups were conducted in three purposefully selected provinces. Quantitative data were analysed using descriptive statistics and qualitative data were analyzed thematically. The innovation implementation framework guided the study. RESULTS: After 3 years of introduction, 82.5% of provinces had established the CDCs. Implementation of CDC establishment policy was influenced by 1) management support; 2) alignment between policy and practice; 3) values towards CDC,; and 4) implementation climate. Other external key influencers included political, social, and cultural factors. CONCLUSION: Our study provides a framework and evidence to guide future inquiry into the factors that affect the relationship between policy implementation and other contextual factors in healthcare organizations.