OBJECTIVES Human papillomavirus (HPV) vaccines offer primary prevention of HPV-related pre-cancers and cancers. AS04-adjuvanted HPV-16/18 vaccine (AS04v) has shown high efficacy (efficacy irrespective of the HPV type) in cervical high grade lesions (CIN2+, CIN3+). The objective of this study is to estimate overall impact on cervical cancer (CC) burden expected from AS04v in the Iberian Peninsula (Spain and Portugal). METHODS Potential decline in CC cases resulting from women vaccination with AS04v was estimated using a previously published model. Model outcomes considered were estimated based on number of CC cases avoided associated with HPV specific CC incidence (HPV-16/18 cases and irrespective of HPV type). Vaccine effectiveness (VE, end-of-study analysis HPV-008 trial) against HPV-16/18 was set at 100% weighted with HPV-16/18 incidence reported in CC in Spain & Portugal. VE irrespective of HPV type was set at 93%. Vaccination coverage was varied from 0% to 100%. Incremental number of cases avoided HPV-16/18 related and irrespective of HPV type were calculated. Potential costs avoided were also estimated based on published lifetime CC costs. RESULTS Through vaccination considering VE irrespective of type and 70% vaccination coverage, AS04v could avoid an additional 206 CC cases in Portugal and 626 CC cases in Spain compared with 412 and 1.009 cases, respectively, due to 16/18 HPV types. VE against non-vaccine types increased the estimated potential number of CC cases prevented by 33% and 38% in Portugal and Spain, respectively. Associated cost avoided due to reduced CC treatment could reach 1.536.644€ in Portugal and 6.374.865€ in Spain (33% and 38% due to overall efficacy respectively). Cases avoided may increase linearly with increasing vaccination coverage. CONCLUSIONS HPV vaccination could considerably contribute to reducing the burden of cervical cancer in Spain and Portugal. AS04v offers potential broad protection and could maximize disease burden reduction due to non-vaccine type VE.