A vaccine-derived poliovirus (VDPV) was isolated in an acute flaccid paralysis (AFP) case reported from Ile-Ife, in Osun state, Southwest Nigeria. We investigated the epidemiological characteristics of the polio event and described the immediate public health response that followed. We interviewed the primary caregiver of the case and conducted active case searches for additional AFP cases in the communities in Ife East Local Government Area (LGA) of Osun state. Stool samples of contacts and non-contacts were collected and sent for laboratory investigation. A public health response with mass supplementary immunization in the affected areas followed immediately in the ward the case was located in October 2015. Also, we reviewed the administrative record of the oral polio vaccine (OPV) coverage in the LGA in the previous four years. The VDPV case was a female, one-month-old child with adequate vaccination history for her age. However, the environment of the child was relatively filthy with inappropriate facilities. Laboratory reports from contact samples were negative for VDPV or any polio isolates. A missed AFP case was found from active case searches and a high proportion of under-five children was immunized with tOPV. The OPV3 administrative coverage in the LGA peaked in 2014 (103%) and dropped in 2015 (67%). Efforts directed toward improving environmental hygiene in households and improving OPV coverage in subsequent routine and supplementary immunization are suggested.