A large number of World Trade Center (WTC) rescue and recovery workers are affected by asthma. While physical and mental health comorbidities have been associated with poor asthma control in this population, the potential role of allergen sensitization is unknown. This study examined the association of indoor sensitization and exposure as a risk factor for increased asthma morbidity in WTC workers. We used data from a prospective cohort of 331 WTC workers with asthma. Sensitization to indoor allergens was assessed by measurement of antigen-specific serum immunoglobulin E (IgE) levels. We used validated tools to evaluate the exposure to indoor allergens. Asthma morbidity outcomes included level of control (Asthma Control Questionnaire, ACQ), quality of life (Asthma Quality of Life Questionnaire, AQLQ) and acute resource utilization. The prevalence of sensitization to cat, dog, mouse, dust mite, cockroach, and mold allergens were 33%, 21%, 17%, 40%, 17%, and 17%, respectively. Unadjusted and regression analyses showed no significant relationship between sensitization and increased asthma morbidity (p > 0.05 for all comparisons), except for sensitization to Aspergillus Fumigatus, cat and mouse epithelium, which were associated with decreased morbidity.