Knock is a major problem when running combined heat and power (CHP) gas engines because of the variation in the network natural gas composition. A curative solution is widely applied, using an accelerometer to detect knock when it occurs. The engine load is then reduced until knock disappears. The present paper deals with a knock preventive device. It is based on the knock prediction following the engine operating conditions and the fuel gas methane number, and it acts on the engine load before knock happens. A state of the art about knock prediction models is carried out. The maximum of the knock criterion is selected as knock risk estimator, and a limit value above which knock may occur is defined. The estimator is calculated using a two-zone thermodynamic model. This model is specifically based on existing formulas for the calculation of the combustion progress, modified to integrate the effect of the methane number. A chemical kinetic model with 53 species and 325 equilibrium reactions is used to calculate unburned and burned gases composition. The different parameters of the model are fitted with a least squares method from an experimental data base. Errors less than 8% are achieved. The knock risks predicted for various natural gases and operating conditions are in agreement with previous work. Nevertheless, the knock risk estimator is overestimated for natural gases with high concentrations of inert gases such as nitrogen and carbon dioxide. The definition of a methane number limit based on the engine manufacturer's recommendation is then required to eliminate unwarranted alerts. Safe operating conditions are thus calculated and gathered in the form of a map. This map, combined with the real time measurement of the fuel gas methane number, can be integrated to the control device of the CHP engine in order to guarantee a safe running towards fuel gas quality variation.