OBJECTIVES: Quadrivalent human papillomavirus (qHPV) vaccine prevents from genital warts in addition to HPV-related cancers. Study objective was to provide first estimates of savings offered by the reduction in GW incidence observed in Belgium, 4 years after the introduction of the qHPV vaccine. METHODS: A retrospective observational study was performed using the MLOZ healthcare insurance database. Number of GW was described by age-group, gender, between 2003 and March 2011. GW cumulative incidence estimates were compared between women vaccinated or not with qHPV vaccine from 2007 onwards. Analyses were restricted to age-groups of women likely to have been vaccinated. Direct medical treatment costs published were updated to €2010 using the purchasing parity power conversion rates method and estimated at 324.2€/case (public healthcare payer perspective). RESULTS: A total of 55,193 women aged 16-20 year-old were retrieved, of whom 13,117 were vaccinated with qHPV vaccine. Within this age-group, 435 first GW cases were observed, 423 in the control group (non vaccinated: 1.01%) and 12 in the vaccinated group (0.09%), representing 920 GW cases/100,000 vaccinated women avoided among this age group during a limited period of 4 years. Cumulative incidence estimates of GW were also significantly lower among women vaccinated with qHPV vaccine compared to those that were not: 0.12% (CI: 0.07%-0.23%) vs. 0.93% (CI: 0.85%-1.03%), relative reduction (RR): -87.1%, p<0.0001. Among girls aged 16-20 and over 4 years, direct healthcare cost saved were estimated at 298K€/100,000 vaccinated girls. CONCLUSIONS: This preliminary analysis suggests that a marked reduction of GW and related resources used in Belgium may be achievable through qHPV vaccination. The reduction of GW and associated treatments costs would be higher if more cohorts were considered and should become more prominent in the coming years when the current and future qHPV vaccinated cohorts will enter into the peak age of risk for GW.