Atypical squamous cells of undetermined significance (ASC-US) are the most common abnormal cytological result on Papanicolaou (Pap) smear. We analyzed four management strategies in a hypothetical cohort of women divided by age group: (1) immediate colposcopy, (2) repeat cytology after an ASC-US Pap smear result, (3) conventional Pap with reflex human papillomavirus (HPV) testing, and (4) liquid-based cytology with reflex HPV testing. Parameter variables were collected from previously published data. Strategies that included reflex HPV testing had the lowest overall costs for all age groups combined. Repeat Pap smears had the highest number of true positive results throughout all stages but also had the uppermost number of missed cancers and highest costs. Immediate colposcopy had the second highest overall costs and detected fewer true positive results than liquid-based cytology. Younger women (aged 18-24 yr) consistently had higher total costs for all strategies investigated. Using the incremental cost-effectiveness (CE) ratio, the immediate colposcopy strategy was more costly and less effective than liquid-based cytology and, therefore, was dominated. The incremental CE ratio was lowest for liquid-based cytology compared with conventional cytology and liquid-based cytology with reflex HPV testing was the most cost-effective strategy.