Objective. To determine the prevalence of HR- HPV DNA in ASC- US Pap smears following implementation of the Bethesda 2001 classification system. Methods. A computer database of Pap smears obtained within Department of the Army medical facilities was queried for the study period August 2002 to June 2004. All ASC- US Pap smears that underwent reflex testing for HR- HPV DNA were included. Additional clinical and demographic data were obtained from facilities within the US northeast region to evaluate the differences in ASC- US and SIL rates between the current and former Bethesda classification systems. Results. 550,000 Pap smears were collected during the study period. The HR- HPV prevalence was 40.8% (95% confidence interval [CI] = 40.3 to 41.3) among 40,870 patients with ASC- US Pap smears. Within the northeast region, the HR- HPV prevalence in ASC- US Pap smears decreased from 61.2% (95% CI = 57.4 to 64.8% ) in patients 18- 22 years old to 24.9% (95% CI = 23.1 to 26.8% ) in patients age 29 and older. When comparing the two classification systems, significant increases in both ASC- H and SIL and decreases in ASC- US were appreciated after the institution of Bethesda system 2001. Conclusion. In our large, diverse cohort, the implementation of the Bethesda II system has resulted in a decrease in ASC- US Pap smear results. Additionally, the prevalence of HR- HPV in theASC- US population was 40.8% , significantly lower than the rate noted in the ALTS trial under the Bethesda I classification system. Objective. To determine the prevalence of HR-HPV DNA in ASC-US Pap smears following implementation of the Bethesda 2001 classification system. Methods. A computer database of Pap smears obtained within Department of the Army medical facilities was queried for the study period August 2002 to June 2004. All ASC-US Pap smears that underwent reflex testing for HR- HPV DNA were included within the US northeast region to evaluate the differences in ASC- US and SIL rates between the current The HR-HPV prevalence was 40.8% (95% confidence interval [CI] = 40.3 to 41.3) among 40,870 patients with ASC-US Pap smears. the northeast region, the HR- HPV prevalence in ASC- US Pap smears decreased from 61.2% (95% CI = 57.4 to 64.8%) in patients 18-22 years old to 24.9% (95% CI = 23.1 to 26.8%) in patients a When comparing the two classification systems, significant increases in both ASC-H and SIL and decreases in ASC-US were appreciated after the institution of Bethesda system 2001. Conclusion. In our large, diverse cohort, the implementation of the Bethesda II system has resulted in a decrease in ASC-US Pap smear results. Additionally, the prevalence of HR-HPV in the ASC-US population was 40.8% significantly higher than the rate noted in the ALTS trial under the Bethesda I classification system.