Anterior pituitary dysfunction is one of the major causes of disability and morbidity in patients suffering from traumatic brain injury (TBI). The present study was undertaken to evaluate the incidence of anterior pituitary dysfunction in cases of moderate and severe TBI, its value in long term prognostication and the factors which predispose to a higher incidence of anterior pituitary dysfunction in acute and chronic phases. This was a prospective cohort study wherein 216 patients with moderate and severe TBI were evaluated within 72 hours of TBI (acute phase) and at 6 months (chronic phase). At 6 months, out of the 216 patients, 95 patients had expired and 35 patients had lost follow-up. The remaining 86 patients were evaluated at 6 months. In the acute phase, hypopituitarism was seen in 82.4% patients, thyroid axis deficiency was seen in 57.4% patients, gonadal axis deficiency in 54.2% patients and adrenal axis deficiency in 13.8% patients. In the chronic phase, hypopituitarism was seen in 59.3% patients, thyroid axis deficiency was seen in 24.4% patients, gonadal axis deficiency in 32.6% patients and adrenal axis deficiency in 23.3% patients. Patients with thyroid axis deficiency at admission had significant association with a bad modified Rankin Scale (mRS) score at 6 months. Thyroid and gonadotropin axes were most commonly affected and deficiency of at least one axis was found in 82.4% patients in the acute phase and 59.3% in the chronic phase. Thyroid axis deficiency had a negative impact on prognosis in post-TBI patients.