Aims: To develop a model, based on microbiological principles, to safely optimize steam sterilization processes. Methods and Results: The minimum exposure time F for a decontamination process at a certain temperature is usually calculated from an empirical model with the decimal reduction time D and the temperature resistance coefficient z as parameters. These are implicitly assumed to be independent of temperature. Using a microbiological approach, it is shown that also D and z depend on temperature, indicating that the usual models provide only reliable results in a limited temperature region. The temperature dependence of F resulting from this approach describes the available experimental data very well. Safety margins to assure sterility can be included in a straightforward way. Conclusions: The results from the present approach can be used to safely optimize decontamination processes. The corresponding mathematical model can be implemented rather directly in process control systems. Significance and Impact of the Study: Our results show that for steam sterilization and disinfection processes the values of F predicted by the usual models largely underestimate the required minimum exposure times at temperatures below 120 degrees C. This has important consequences for the optimization of such processes.