Human health is adversely affected by ozone and the volatile organic compounds (VOCs) produced from its reactions in the indoor environment. Hence, it is important to characterize the ozone‐initiated reactive chemistry under indoor conditions and study the influence of different factors on these reactions. This investigation studied the ozone reactions with clothing through a series of experiments conducted in an environmental chamber under various conditions. The study found that the ozone reactions with a soiled (human‐worn) T‐shirt consumed ozone and generated VOCs. The ozone removal rate and deposition velocity for the T‐shirt increased with the increasing soiling level and air change rate, decreased at high ozone concentrations, and were relatively unaffected by the humidity. The deposition velocity for the soiled T‐shirt ranged from 0.15 to 0.29 cm/s. The ozone‐initiated VOC emissions included C6–C10 straight‐chain saturated aldehydes, acetone, and 4‐OPA (4‐oxopentanal). The VOC emissions were generally higher at higher ozone, humidity, soiling of T‐shirt, and air change rate. The total molar yield was approximately 0.5 in most cases, which means that for every two moles of ozone removed by the T‐shirt surface, one mole of VOCs was produced.