The mainly factors studied to predict fatigue life of hot mix asphalt-HMA in flexible pavements are the loading effect, type of test, compaction methods, design parameters of HMA (e.g., particle size and size distribution curve, fine content, type of bitumen) and the variables associated with the environment (mainly moisture, temperature, aging). This study evaluated through a computer simulation, the influence of the granular layers and subgrade on the fatigue life of asphalt layers in flexible pavement structures. Mechanics parameters of granular layers of subgrade, base and subbase were obtained using the mathematical equations currently used for this purpose in the world. The emphasis of the study was the city of Bogota, where the average annual temperature is 14°C and soils predominantly clay, generally experience CBR magnitudes between 1% and 4%. General conclusion: stiffness of the granular layers and subgrade significantly affect the fatigue resistance of HMA mixtures. Likewise, the use of different equations reported in reference literature in order to characterize granular layers may vary the fatigue life between 4.6 and 48.5 times, varying the thickness of the pavement layers in the design.