Infant mortality rate (IMR) is one of the most important development indicators. In India, there is a severe interstate disparity regarding IMR. Kerala registers a very low IMR; whereas in Odisha it is pretty high. It is somewhat paradoxical as Odisha fares substantially better than many other states with lower IMR regarding total fertility rate, antenatal care and in many other aspects. The present article attempts to investigate the applicability of usually perceived major determinants of IMR as evidenced in the existing literature for Odisha. The panel data multiple regression carried out with data of 30 districts of Odisha over three years indicates that physiological and behavioural factors together with maternal and demographic factors are perhaps more important than the health programmes for reduction of IMR in Odisha. Moreover, many of the usually perceived major determinants of IMR including economic betterment are statistically insignificant for Odisha. The policymakers should take into account these facts and instead of a series of health programmes, they might resort to awareness building regarding breastfeeding and birth spacing. Mother’s nutritional status should also be strengthened so that they can sustain exhaustive breastfeeding for first six months after the birth of the child.