To describe the process and challenges in the roll out of a large cervical cancer vaccination program to protect against human papilloma virus (HPV) infection. This article describes the process of planning and implementing a HPV vaccination program using the existing state-wide framework that supports vaccine delivery to all 219 high schools in South Australia. The decision was made to offer three doses of HPV vaccine to 50,191 female students in Years 8-12 during the 2007 school year. By November 2007, despite many challenges, the school vaccination program had delivered 107,541 doses of HPV vaccine. Coverage of dose 1 was highest in Years 8 (83%) and 10 (70%), but was reduced for doses 2 and 3 in all year levels, with dose 3 coverage ranging from 55% (Year 11) to 77% (Year 8). The introduction of a large school-based vaccination program at short notice posed new challenges for the co-ordination and implementation. Not all schools supported the introduction of HPV vaccine, resulting in reduced access for some students. Negative media messages provided a strong platform for individuals who opposed vaccination. These factors may have contributed to the less-than-expected uptake of HPV vaccine. Historically, there has been high uptake of other vaccines given to adolescents. However, the introduction of HPV vaccine may have adversely affected the uptake of Hepatitis B vaccine, given concurrently in the school program. Further studies are needed to determine if this is likely to have a negative effect on the public perception of the value of vaccine programs in general.