In order to improve the properties of calcium sulfate anhydrous whisker (ACSW) and polyester fiber composite reinforced asphalt mixture (ACPRA) to meet the service requirements of pavement materials in low-temperature environments, the central composite circumscribed design (CCC), a kind of response surface methodology, was chosen to optimize the design parameters. Three independence variables, asphalt aggregate ratio, ACSW content, and polyester fiber content were adopted to evaluate the design parameters. Four responsive variables, air voids, Marshall stability, splitting tensile strength, and failure tensile strain, were chosen to study the volumetric and mechanical characteristics, and the low-temperature behavior of ACPRA by the Marshall test and indirect tensile test at −10 °C. The results showed that, taking low-temperature behavior optimization as the objective, the CCC method was practicable to optimize design of ACPRA, and the optimization design parameters were asphalt aggregate ratio of 4.0%, ACSW content of 10.8%, and polyester fiber content of 0.4%. Furthermore, the impact of three independence variables interactions on four response variables was also discussed, and it was identified that the interaction between asphalt aggregate ratio and ACSW content, and between asphalt aggregate ratio and polyester fiber content, has greater bearing on the splitting tensile strength and failure tensile strain of APCRA. Meanwhile, ACSW and polyester fiber enhancing the low-temperature behavior of APCRA was primarily connected with their contents.
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