This application concerns systems and methods for compressing natural gas with an internal combustion engine. In a representative embodiment, a system for compressing a gas comprises a reciprocating internal combustion engine including at least one piston-cylinder assembly comprising a piston configured to travel in a cylinder and to compress gas in the cylinder in multiple compression stages. The system can further comprise a first pressure tank in fluid communication with the piston-cylinder assembly to receive compressed gas from the piston-cylinder assembly until the first pressure tank reaches a predetermined pressure, and a second pressure tank in fluid communication with the piston-cylinder assembly and the first pressure tank. The second pressure tank can be configured to receive compressed gas from the piston-cylinder assembly until the second pressure tank reaches a predetermined pressure. When the first and second pressure tanks have reached the predetermined pressures, the first pressure tank can be configured to supply gas to the piston-cylinder assembly, and the piston can be configured to compress the gas supplied by the first pressure tank such that the compressed gas flows into the second pressure tank.