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Adult-onset growth hormone deficiency (GHD) has been associated with reduced quality of life (QOL) and neurobehavioral (NB) deficits. This prospective study tested the hypothesis that traumatic brain injury (TBI) patients with GHD or GH insufficiency (GHI) would exhibit greater NB/QOL impairment than patients without GHD/GHI. Complicated mild, moderate, and severe adult TBI patients (GCS score 3–14) had pituitary function and NB/QOL testing performed 6–9 months postinjury. GH-secretory capacity was assessed with a GHRH-arginine stimulation test and GHD and GHI were defined as peak GH <6 or ≤12 ng/mL (5th and 10th percentiles of healthy control subjects, respectively). Of 44 patients (mean age, 32 ± 18 years; median GCS, 7), one (2%) was GHD, seven (16%) were GHI, and 36 (82%) were GH-sufficient at 6–9 months post-injury. Mean peak GH was 8.2 ± 2.1 ng/mL in the GHD/GHI group versus 45.7 ± 29 ng/mL in the GHsufficient group. The two groups were well-matched in injury characteristics, except that one patient with GHD had central hypogonadism treated with testosterone prior to NB/QOL testing. At 6–9 months postinjury, patients with GHD/GHI had higher rates of at least one marker of depression (p < 0.01), and reduced QOL (by SF-36 Health Survey) in the domains of limitations due to physical health (p = 0.02), energy and fatigue (p = 0.05), emotional well-being (p = 0.02), pain (p = 0.01), and general health (p = 0.05). Chronic GHI develops in approximately 18% of patients with complicated mild, moderate, or severe TBI, and is associated with depression and diminished QOL. The impact of GH replacement therapy on NB function and QOL in these TBI patients is being tested in a randomized placebo-controlled trial.