We examined the relationship of pre-injury intelligence, demographic variables, lesion location, brain tissue volume loss and a number of genetic markers to long-term cognitive decline in a group of Vietnam veterans with predominantly penetrating head injury (PHI) suffered more than 30 years ago. Using linear and stepwise regression procedures, we found that those with PHI demonstrated a greater degree of cognitive decline overall during the years following recovery from injury compared with a control group of uninjured Vietnam veterans. This became increasingly significant later in life. We also found that pre-injury intelligence was the most consistent predictor of cognitive outcome across all phases of potential recovery and decline after such injuries. While laterality of lesion was not a factor, we did find some associations between atrophy and specific regions of tissue loss and long-term cognitive functioning. Finally, we found evidence for an association between level of cognitive decline following PHI and the possession of certain genetic markers that have been linked with brain injury and neurodegeneration. Thus exacerbated decline does occur in Vietnam veterans with PHI and it is apparently unrelated to dementia and is determined by multiple factors (most notably pre-injury intelligence).