Hydrogen is considered the most promising future energy carrier, and an internal combustion engine fueled by hydrogen is seen as a bridging technology toward a widespread hydrogen infrastructure. Internal combustion engines allow the use of pure hydrogen, as well as blends of hydrogen and methane, as a fuel. However, hydrogen as an energy carrier has to be produced from other energy sources. The lack of a hydrogen infrastructure currently hinders widespread use of hydrogen as a fuel. In these investigations, we analyze whether a blend of hydrogen (H2) with methane (CH4) could be a viable alternative to pure hydrogen for fueling internal combustion engines. In order to determine the effects of blending H2 with CH4 on engine efficiency and emissions, we conducted tests on an automotive-size, single-cylinder research engine using two different blends of 30- and 65-mass-% CH4 in H2 (5- and 20-vol.-%, respectively) and pure hydrogen as a baseline. We identified the changes to the engine control unit (ECU) of a hydrogen-powered pick-up truck that would be required to allow the engine to operate on the H2/CH4 blends. We then tested the modified truck on a chassis dynamometer to evaluate the influence of using blended fuel on the dynamic behavior over different drive cycles. The steady-state research engine results showed a noticeable decrease in nitric oxide (NOx) emissions and a slight decrease in engine efficiency with the increased amount of CH4. At the same time, carbon-based emissions increased as a result of the additional carbon components in the fuel. While carbon dioxide (CO2) is not produced during combustion of pure H2, blending H2 with CH4 caused a dramatic increase in greenhouse gas emissions, including CO2. Analysis of pressure traces and heat release rates revealed a significant decrease in the combustion rate with the increased methane in the blend. The spark timing map in the truck ECU had to be adapted to compensate for the lower combustion rate that occurs during blended operation (compared with the calibration for pure hydrogen) because of the changes in gas properties. The injection map also had to be adjusted accordingly. The dynamic vehicle results confirmed the findings of the engine tests. These studies contribute to the conclusion that hydrogen is an excellent alternative for fueling internal combustion engines. Its flexibility, in terms of fuel acceptance, is another reason for the hydrogen-fueled internal combustion engine to be considered as a bridging technology toward a sustainable hydrogen infrastructure. Blending hydrogen with methane takes advantage of the unique combustion properties of hydrogen, while at the same time reducing the demand for pure hydrogen.