Recommendations for worldwide use of human papillomavirus (HPV) vaccine are increasing. This study conducted a systematic review of articles related to cost-effectiveness analysis of wide-range HPV vaccination programs compared with Pap smear screening published before August 2007. Eight articles were identified using predefined inclusion and exclusion criteria. After excluding two outliers, the range of incremental cost-effectiveness ratios (ICERs) from six articles is between $16,600 and $27,231 per quality-adjusted life year (QALY) gained. The World Health Organization's guideline that compares incremental cost-effectiveness ratios (ICERs) with per capita Gross Domestic Product (GDP) was used to determine whether nation-wide application of HPV vaccine would be cost-effective. The HPV vaccination program is cost-effective in only 46 countries where per capita GDP is high. Further cost-effectiveness studies in developing and third-world countries are needed for making policy decisions.