A reliability-based mix design and analysis system has been developed for mitigating fatigue distress in asphalt pavements. Design decisions consider not only fundamental mix properties but also the level of design traffic, the temperature environment at the site, the pavement structural section, laboratory testing and construction variabilities, and the acceptable level of risk. This paper describes the mix design and analysis system, discusses its calibration, illustrates its use, and assesses the consistency of current California design practice vis- a-vis the control of fatigue distress. It reveals possible inconsistencies in current California design practice, discusses effects of construction variability, highlights advantages of rich-bottom pavement structures, and illustrates the integration of mix and structural components into a reliability-based mix design process.