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.