From 1991, heavy-duty natural gas vehicles (NGVs) have been supplied as an alternative to diesel heavy-duty vehicles (HDVs) in Korea. In this paper, greenhouse gas (GHG) emissions from heavy-duty NGVs in Korea were estimated using vehicle simulation model. A backward-looking simulation model was used to calculate GHG emissions for 40 cases of heavy-duty NGVs. Based on the simulation results and vehicle statistical data, total GHG emissions from heavy-duty NGVs in Korea were estimated. The results show that annual GHG emissions from heavy-duty NGVs are 1.66 million tons, which makes up 6.75% of total GHG emissions from HDVs. The average GHG emissions of heavy-duty NGVs are 6.3% lower than diesel HDVs of a similar weight level. Each heavy-duty NGV emits 39.3 tons less GHG than a diesel HDV per year.