INTRODUCTION: Vaccination is an effective and proven method of preventing infectious diseases. However, uptake has not been optimal with available vaccines partly due to vaccination hesitancy. Various public health approaches have adressed vaccination hesitancy. Serious video games involving vaccination may represent an innovative public health approach. The aim of this study was to identify, describe, and review existing serious video games on vaccination. METHOD: A systematic review was performed. Various databases were used to find data on vaccination-related serious video games published from January 1st 2000 to May 15th 2015. Data including featured medical and vaccination content, publication characteristics and games classification were collected for each identified serious game. RESULTS: Sixteen serious video games involved in vaccination were identified. All games were developed in high-income countries between 2003 and 2014. The majority of games were available online and were sponsored by educational/health institutions. All games were free of charge to users. Edugame was the most prevalent serious game subcategory. Twelve games were infectious disease-specific and the majority concerned influenza. The main objective of the games was disease control with a collective perspective. Utilization data was available for two games. Two games were formally evaluated. DISCUSSION: The use of serious video games for vaccination is an innovative tool for public health. Evaluation of vaccination related serious video games should be encouraged to demonstrate their efficacy and utility.