Prediction of run-up level is a key task in design of the coastal structures. For the design of the crest level of coastal structures, the wave run-up level with a 2% exceedance probability, R u2% , is most commonly used. In this study, the performance of M5 model tree for prediction of the wave run-up on rubble-mound structures was investigated. The main advantage of model trees, unlike the other soft computing tools, is their easier use and more importantly their understandable mathematical rules. Experimental data set of Van der Meer and Stam was used for developing model trees. The conventional governing parameters were selected as the input variables and the obtained results were compared with Van der Meer and Stam’s formula, recommended by the Coastal Engineering Manual (CEM, 2006). The predictive accuracy of the model tree approach was found to be superior to that of Van der Meer and Stam’s empirical formula. Furthermore, to judge the generalization capability of the model tree method, the model developed based on laboratory data set was validated with the prototype run-up measurements on the Zeebrugge breakwater, Belgium. Results show that the model tree is more accurate than empirical formulas and TS Fuzzy approach in estimating the full-scale run-up.