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Fatigue cracking performance of asphalt mixtures is significantly affected by mixture variables and environmental and loading conditions in the field. Thus, there is a need to understand the effect of critical factors on the fatigue cracking resistance of asphalt mixtures through an extensive study. For this purpose, the present research is focused on characterizing fatigue cracking resistance of asphalt mixtures by considering different factors such as aggregate gradations (two dense and two gap gradations), binder types (two unmodified and three modified binder types), binder content (optimum binder content and optimum binder content ±0.5 %), test temperatures (15°C, 25°C, and 35°C), and three stress levels for different asphalt layer thicknesses (40, 80, 120, 160, 200, and 240 mm). An indirect tensile fatigue test was performed to characterize fatigue cracking resistance of asphalt mixtures, and a Kaplan–Meier survival analysis was carried out to examine whether the factors that were considered significantly affected the fatigue performance. Pavement sections with varying thicknesses of asphalt layers were analyzed using IITPAVE, a pavement analysis software, to compare the mixtures’ fatigue performance. All of the variables taken into consideration in this study were shown to have a statistically significant effect (p value < 0.05). However, the binder type had a stronger influence than the other variables on the resistance to fatigue cracking. Finally, a fatigue life equation (adjusted R2 = 0.77) was developed considering all the mixture combinations, which can be used for determining the laboratory fatigue life of asphalt mixtures.