The 62-year-old Raju breathed his last at 3:40 am after being hospitalised for a brief period, hospital sources said.
Since January this year, he was down with recurring pneumonia and had been admitted to the hospital a week ago for lung infection, sources said.
He is survived by his wife and two daughters.
The soft-spoken Raju was appointed on January 19, 2009, as the first chief of the NIA set up in the wake of the 26/11 Mumbai terror strikes.
A 1975 batch IPS officer of Jammu and Kashmir cadre, Raju handled the case of United States citizen Lashkar-e-Tayiba operative David Headley.
Before being appointed as NIA chief, Raju was the director general (vigilance) of Jammu and Kashmir.
Considered as one of the finest officers, Raju was associated with the probes into the Rajiv Gandhi assassination case, hijacking of an Indian Airlines plane to Kandahar in 1999 and the naval war-room leak.
Serving as head of the vigilance bureau in Jammu and Kashmir earlier, Raju streamlined the department which was in a shambles due to militancy.
His investigation had brought to light the alleged misappropriation by Maulvi Ifthikar Hussain Ansari, a former minister in Mufti Mohammed Sayeed's cabinet.