BACKGROUND: A high-potency monovalent oral type 1 poliovirus vaccine (mOPV1) was developed in 2005 to tackle persistent poliovirus transmission in the last remaining infected countries. Our aim was to assess the efficacy of this vaccine in India. METHODS: We estimated the efficacy of mOPV1 used in supplementary immunisation activities from 2076 matched case-control pairs of confirmed cases of poliomyelitis caused by type 1 wild poliovirus and cases of non-polio acute flaccid paralysis in India. The effect of the introduction of mOPV1 on population immunity was calculated on the basis of estimates of vaccination coverage from data for non-polio acute flaccid paralysis. FINDINGS: In areas of persistent poliovirus transmission in Uttar Pradesh, the protective efficacy of mOPV1 was estimated to be 30% (95% CI 19-41) per dose against type 1 paralytic disease, compared with 11% (7-14) for the trivalent oral vaccine. 76-82% of children aged 0-23 months were estimated to be protected by vaccination against type 1 poliovirus at the end of 2006, compared with 59% at the end of 2004, before the introduction of mOPV1. INTERPRETATION: Under conditions where the efficacy of live-attenuated oral poliovirus vaccines is compromised by a high prevalence of diarrhoea and other infections, a dose of high-potency mOPV1 is almost three times more effective against type 1 poliomyelitis disease than is trivalent vaccine. Achieving high coverage with this new vaccine in areas of persistent poliovirus transmission should substantially improve the probability of rapidly eliminating transmission of the disease.