Despite the frequent occurrence of vehicle fires, very few studies investigating firefighters' potential inhalation exposures during vehicle fire suppression have been conducted. In this paper, we present an assessment of firefighters' health risk from vehicle fire suppression that accounts for the mixture of gases and vapors likely to be found in these fires. Summa canisters were used to collect emissions from the engine and cabin fires of a single vehicle and were analyzed for 75 volatile organic compounds (VOCs). Firefighters' breathing zone concentrations (BZCs) of aromatic hydrocarbons, aldehydes, isocyanates, and carbon monoxide were measured during the suppression of three vehicle fires. The Summa canister and BZC data were used to develop a simple model for predicting BZCs for the compounds that were not measured in the firefighters' breathing zones. Hazard quotients (HQs) were calculated by dividing the predicted and measured BZCs by the most conservative short-term exposure limits (STELs) or ceiling limits. Hazard indices (HIs) were determined by adding HQs for compounds grouped by the target organ for acute health effects. Any HIs above unity represented unacceptable risks. According to this mixture analysis, the estimated 95(th) percentile of the exposure distribution for the study population represents ≥ 9.2 times the acceptable level of risk to the respiratory tract and eyes. Furthermore, chemicals known or reasonably anticipated to be human carcinogens contributed to > 45% of these HIs. While STELs are not usually based on carcinogenicity, maintaining exposures below STELs may protect individuals from the biological stress that could result from short-term exposures to carcinogens over time. Although vehicle fires are suppressed quickly (<10 min), this assessment suggests that firefighters have the potential to be overexposed to acute toxins during vehicle fire suppression and should therefore wear self-contained breathing apparatus at all times during vehicle fire response.