A relatively complete procedure for high cycle fatigue life assessment of the engine components is outlined in the present paper. The piston is examined as a typical component of the engine. In this regard, combustion process and transient heat transfer simulations, determination of the instantaneous variations of the pressure and temperature in the combustion chamber, kinematic and dynamic analyses of the moving parts of the engine, thermoelastic stress analyses, and fatigue life analyses are accomplished. Results of the simulation are compared with the test data to verify the results. The heat transfer results are validated by the experimental results measured by the Templugs. The nonlinear multipoint contact constraints are modeled accurately. Results of the more accurate available fatigue criteria are compared with those of a fatigue criterion recently proposed by the first author. These results are also evaluated by comparing them with the experimental durability tests. The presented procedure may be used, e.g., to decide whether it is suitable to convert a gasoline-based engine to a bi-fuel one. Results of the various thermomechanical fatigue analyses performed reveal that the piston life decreases considerably when natural gas is used instead of gasoline.