Quantitative structure-property relationship (QSPR) approaches were applied as a tool for assessment of the standard enthalpy of formation of 40 organic azido compounds with different molecular structure which are used as energetic plasticizers in energetic material formulations. Chemical structures of these compounds were encoded into several sets of molecular descriptors, which represent various physical and chemical properties of these molecules. A total number of 1475 molecular descriptors of 22 different types were selected and calculated. Then a stepwise regression method was applied to determine the most relevant molecular descriptors which have significant effects on the Delta H degrees(f) of azido compounds. Finally, the best subsets regression method and also the response plot of PLS regression is used to evaluate the predictive power of the selected molecular descriptors and find out the possibility to reduce the dimension of the initially developed model. The finally derived models displayed a good predictive ability arising from the determination coefficient corresponding to the leave one out (LOO) cross validation technique (R-2=0.9821, 0.9962 and QLOO2=0.9907, 0.9851 respectively). Moreover, the obtained results of this investigation are compared with results which have been calculated using "Energetic Materials Designing Bench (EMDB), Version 1.0" software package.