Objective: A positive association between mental health conditions and poor asthma control has been documented in the World Trade Center-exposed population. Whether factors such as medication adherence mediate this association is unknown. Methods: The study population was drawn from adult participants of the World Trade Center Health Registry Cohort who self-reported as asthmatic after the disaster and who were currently prescribed a long-term control medication (LTCM). Multivariable linear regression was used to estimate the associations between mental health condition (PTSD, depression, or anxiety) and continuous adherence and Asthma Control Test (ACT) scores. Results: In the study sample of 1,293, 49% were not adherent to their LTCM and two thirds reported poorly or very poorly controlled asthma. Presence of any mental health condition was associated with a 2-point decline in ACT and half a point decrease in adherence scores. However, in the multivariable model, better adherence was statistically significantly associated with slightly worse control. Conclusions: The total effect of mental health on asthma control was opposite in sign from the product of the paths between mental health and adherence and adherence and asthma control; we therefore found no evidence to support the hypothesis that adherence mediated the negative association between poor mental health and adequate asthma control. More research is needed to understand the complex causal mechanisms that underlie the association between mental and respiratory health.