Anxiety and depression symptoms are commonly experienced after traumatic brain injury (TBI). However, studies validating measures of anxiety and depression for this population are scarce. Using novel indices derived from symmetrical bifactor modeling, we evaluated whether the Hospital Anxiety and Depression Scale (HADS) reliably differentiated anxiety and depression in 874 adults with moderate-severe TBI. The results showed that there was a dominant general distress factor accounting for 84% of the systematic variance in HADS total scores. The specific anxiety and depression factors accounted for little residual variance in the respective subscale scores (12% and 20%, respectively), and overall, minimal bias was found in using the HADS as a unidimensional measure. Further, in a subsample of 184 participants, the HADS subscales did not clearly discriminate between formal anxiety and depressive disorders diagnosed via clinical interview. Results were consistent when accounting for degree of disability, non-English speaking background, and time post-injury. In conclusion, variance in HADS scores after TBI predominately reflects a single underlying latent variable. Clinicians and researchers should exercise caution in interpreting the individual HADS subscales and instead consider using the total score as a more valid, transdiagnostic measure of general distress in individuals with TBI.