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Secondhand exposure to environmental tobacco smoke (ETS) in multifamily housing remains a health concern despite strong recommendations to implement non-smoking policies. Multiple studies have documented exposure to ETS in non-smoking units located in buildings with smoking units. However, characterizing the magnitude of ETS infiltration or measuring the impact of building interventions or resident behavior on ETS is challenging due to the complexities of multifamily buildings, which include variable resident behaviors and complex airflows between numerous shared compartments (e.g., adjacent apartments, common hallways, elevators, heating, ventilating and air conditioning (HVAC) systems, stack effect). In this study, building simulation models were used to characterize changes in ETS infiltration in a low income, multifamily apartment building in Boston which underwent extensive building renovations targeting energy savings. Results suggest that exterior wall air sealing can lead to increases in ETS infiltration across apartments, while compartmentalization can reduce infiltration. The magnitude and direction of ETS infiltration depends on apartment characteristics, including construction (i.e., level and number of exterior walls), resident behavior (e.g., window opening, operation of localized exhaust fans), and seasonality. Although overall ETS concentrations and infiltration were reduced post energy-related building retrofits, these trends were not generalizable to all building units. Whole building smoke-free policies are the best approach to eliminate exposure to ETS in multifamily housing.