Chlorination is the most widely used method for disinfection of drinking water, but there are concerns about the formation of by-products, such as trihalomethanes (THMs), since the chronic exposure to them may pose risks to human health. For these reasons regulations fix maximum acceptable THMs levels throughout distribution networks, so it is very important to be able to correctly reproduce their formation. In the literature many models for predicting THMs formation have been developed, both based on empirical relationships and on kinetics involved during chlorine reactions. In this work the use of some of these models and their reliability in real situations is investigated through the application to the Aurunci-Valcanneto Water Supply System in Southern Lazio (Italy). The comparison of the performances of 18 selected literature empirical models furnishes interesting observations, indicating that the formula, developed using field data, results in being more suitable for reproducing THMs formation for the presented case study. Other considerations are also offered from the comparison with the results obtained using a simple first order kinetic model, calibrated using measured data.