The use of natural gas in medium and heavy duty engines for public transportation is a promising way for reducing exhaust emissions. Computer simulations, coupled with engine tests, have arisen as a valuable methodology to study the gas exchange processes inside intake and exhaust manifolds. A wave action model is set up in order to simulate a natural gas fuelled turbocharged engine. Once the modeling results show good agreement when comparing with measured data at different running conditions in terms of fluid dynamic properties, the model is used to study the air-fuel mixture process in the intake manifold and optimize the injection system behavior. Comparisons of modeled air-fuel composition in the cylinders are performed with both single and multi-point injection strategies. These cylinder to cylinder air-fuel mixture dispersion problems are analyzed at both steady and transient engine running conditions. Steady operation is performed correctly when using single-point injection since the gas mixer upstream the throttle valve enhances the mixing process. However, significant gas dispersion among cylinders appears during an engine load transient. With multi-point injection the critical parameter is the injection timing, since it is usually larger than the intake stroke period and, if it is not conveniently arranged, significant natural gas dispersion among cylinders may appear at both steady and transient running conditions.