Cement concrete has always played an essential role in the general development of the construction industry. Many studies improve the properties and durability of cement concrete by adding chemical additives and mineral additives. One of them, fly ash, is one of the most preferred applied mineral additives. Currently, the demand for fly ash is becoming an urgent problem, as it is also can reduce environmental pollution from by-products of thermal power plants not only in Vietnam but also all around the world. To evaluate the factors affecting compressive strength of concrete, such as fly ash, type of cement used, date and designed concrete grade, we based our study on the design of experiment (DOE). The influencing variables have different levels of investigation, which are based on previous studies. With the useful statistical analysis tools, the number of experiments, and the results of the experimental analysis, we can see the influence of each element and their interaction on the compressive strength of the concrete. On that basis, it is possible to choose the option with reasonably selected ingredients to achieve the expected optimal compressive strength.