We compared the histologic follow-up of 368 smears or slides with an interpretation of “atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion” (ASC-H) based on conventional and liquid-based preparations and age groups in a high-risk population. Patients with an ASC-H interpretation were 17 to 87 years old (mean, 36.8 years). The specimens were 52 liquid-based preparations and 316 conventional smears. For 218 cases (59.2%), including 28 liquid-based preparations (65%) and 190 conventional smears (58%), histologic follow-up was available. In 20 liquid-based preparations (71%) and 152 conventional smears (80.0%), cervical intraepithelial neoplasia (CIN) or higher was revealed on subsequent biopsy. Other results were as follows: liquid-based preparations, CIN1, 11 (55%); CIN2/3, 9 (45%); conventional smears, CIN1, 78 (51.3%); CIN2/3, 70 (46.1%); squamous cell carcinoma, 4 (2.6%). There was no statistically significant difference in the incidence of CIN or higher on subsequent biopsy after an interpretation of ASC-H based on preparation types. The incidences of CIN in patients 40 years old or older and patients younger than 40 years were 66% and 84%, respectively, a statistically significant difference. Because of the high incidence of clinically significant lesions noted on subsequent follow-up, patients with an interpretation of ASC-H should be observed closely and referred for colposcopic examination regardless of their age.