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Mechanical ventilation systems are used in residences to introduce ventilation air and dilute indoor-generated pollutants. A variety of ventilation system types can be used in home retrofits, influencing indoor air quality (IAQ) in different ways. Here we describe the Breathe Easy Project, a >2-year longitudinal, pseudo-randomized, crossover study designed to assess IAQ and adult asthma outcomes before and after installing residential mechanical ventilation systems in 40 existing homes in Chicago, IL. Each home received one of three types of ventilation systems: continuous exhaust-only, intermittent powered central-fan-integrated-supply (CFIS), or continuous balanced system with an energy recovery ventilator (ERV). Homes with central heating and/or cooling systems also received MERV 10 filter replacements. Approximately weeklong field measurements were conducted at each home on a quarterly basis throughout the study to monitor environmental conditions, ventilation operation, and indoor and outdoor pollutants, including size-resolved particles (0.3-10 μm), ozone (O 3 ), nitrogen dioxide (NO 2 ), carbon dioxide (CO 2 ), carbon monoxide (CO), and indoor formaldehyde (HCHO). Mean reductions in indoor/outdoor (I/O) ratios across all systems after the intervention were approximately 12% (p = 0.001), 10% (p = 0.008), 42% (p < 0.001), 39% (p = 0.002), and 33% (p = 0.007), for CO 2 , NO 2 , and estimated PM 1 , PM 2.5 , and PM 10 , respectively. There was a reduction in I/O ratios for all measured constituents with each type of system, on average, but with varying magnitude and levels of statistical significance. The magnitudes of mean differences in I/O pollutant concentrations ratios were generally largest for most pollutants in the homes that received continuous balanced with ERV and smallest in the homes that received intermittent CFIS systems, with apparent benefits to providing ventilation continuously rather than intermittently. All ventilation system types maintained similar indoor temperatures during pre- and post-intervention periods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)