Although HIV prevalence has increased in most-at-risk populations (MARPs) across Nigeria, effective programming was difficult because Nigeria lacked information for prevention programmes to target interventions that maximise coverage and cost effectiveness. Epidemic appraisals (EA) were conducted in eight states to provide evidence for the planning, implementation and co-ordination of prevention interventions. Component 1: Mapping determined the size, typology and locations of MARPs. Component 2:Venue profiling identified and profiled venues where general populations engaged in high-risk behaviours. Component 3: Rural appraisals provided insights into risk behaviours and sexual networking in villages. States used mapping results to prioritise areas with a MARP coverage of 70% – 80% and then scale up interventions for non-brothel-based female sex workers (FSWs) instead of focusing on brothel-based FSWs. The eight states prioritised funding for the high-coverage areas to ensure a minimum coverage level of 70% – 80% of MARPs was reached. The refocused resources led to cost efficiencies. Applying venue profiling results, six states implemented interventions at bars and night clubs – previously not covered. States also maximised intervention coverage for high-risk general populations; this led to the use of resources for general population interventions in a focused way rather than across an entire state. States focused on condom programmes in rural areas. EA results provided the evidence for focusing interventions for high MARP coverage as well as for high-risk general populations. The states applied the results and rapidly refocused their interventions, increasing the likelihood of having an impact on HIV transmission in those states. Nigeria is now implementing EAs in the remaining 29 states to effect national-level impact.