Between June and October 2005, 45 laboratory-confirmed type 1 vaccine-derived poliovirus (VDPV) cases were identified on Madura Island in Indonesia. Genetic sequencing data on VDPV isolates were consistent with replication and circulation for up to approximately 2 years. Concurrent circulation with type 1 wild poliovirus (WPV) enabled comparisons of VDPV and WPV cases and found that clinical and epidemiological features of both were similar. Attack rates for VDPV were as high as those for WPV. Of 41 VDPV case patients with known vaccination status, 25 (61%) had received zero oral polio vaccine (OPV) doses. Low population immunity due to low routine OPV coverage in rural areas and the absence of WPV circulation for more than a decade were major predisposing factors for the emergence of VDPV. Suboptimal surveillance and a limited initial immunization response may have contributed to widespread circulation. Sensitive surveillance and prompt high-quality immunization responses are recommended to prevent the spread of VDPVs.