In order to mitigate carbon dioxide (CO₂) emissions, policy action that addresses vehicle emissions is essential. While many previous studies have focused on light-duty vehicles (LDV), little is known about medium- and heavy-duty vehicles (MHDV). This study lays the groundwork for future MHDV investigations in the Republic of Korea by developing an MHDV CO₂ emissions inventory. The bottom-up approach was used to calculate national CO₂ emissions. Simulation methods that calculated the CO₂ emissions of each vehicle and statistical data, such as vehicle miles traveled (VMT) and the number of registered vehicles were used to predict CO₂ emissions. The validity of this simulation model was examined by comparing it with the chassis dynamometer test results. The results of this study showed that the CO₂ emissions of MHDV in 2015 were 24.47 million tons, which was 25.5% of the total road transportation CO₂ emissions, despite only comprising 4.2% of the total vehicles. Trucks emitted 69.6% and buses emitted 30.4% of the total MHDV CO₂ emissions. Using the results between 2012 and 2015, the level of business-as-usual (BAU) CO₂ emissions will be 25.37 million tons in 2020.