AbstractRepetitive loads result in increased irrecoverable strain and, consequently, fatigue cracking failure. Fatigue resistance is the prime factor controlling the service life of the concrete pavements. This research study utilized natural rubber latex (NRL) to enhance the mechanical strength and flexural fatigue resistance of normal concrete. The effect of influence factors, such as water to cement (w/c) and dry rubber to cement (r/c) ratios, on the compressive and flexural strengths and flexural fatigue behavior was studied. Normal and NRL concretes were subjected to compressive, flexural, and flexural fatigue tests. At all w/c ratios, a higher r/c ratio resulted in a lower compressive strength but higher flexural strength. The highest flexural strength was found at the optimum r/c ratios of 0.58, 1.16, and 1.73 for w/c=0.3, 0.4, and 0.5, respectively. Concrete modified by NRL at the r/c ≤ optimum ratio had lower plastic deformation than normal concrete at the same applied flexural stress, hence, higher fatigue life (Nf). As a result, the NRL-concrete pavement at the optimum r/c ratio was found to have a thinner thickness than the normal concrete pavement for the same traffic load conditions at the same service life, which can reduce the operational cost. A cost-effective mix design method of NRL-concrete pavement with the optimized construction (operation and material) cost was also recommended. The outcomes of this research will facilitate the utilization of the NRL additive alternative to synthetic polymer for sustainable NRL-concrete pavement in Thailand and other Southeast Asian and South American countries, which are major global producers of natural rubber.