Objective: Age-adjusted evaluations have explored the possible utility of human papillomavirus (HPV) test results in women with low-grade squamous intra-epithelial lesion (LSIL) Paps. We document LSIL correlation data with HPV test results and histopathologic follow-up from a large academic women’s hospital practice. Study Design: LSIL Pap tests with intermediate-/high-risk HPV DNA testing between July 1, 2005 and April 30, 2008 were studied along with follow-up histopathologic diagnoses. Patients were divided into age groups, and tissue diagnoses were correlated with HPV test results. Results: 1,083 (80.2%) of a total of 1,351 LSIL Pap samples tested HPV positive. HPV prevalence declined in older age groups. 719 women with LSIL Pap and HPV test results had at least 1 follow-up cervical biopsy result. 89 of 612 patients with HPV-positive LSIL (14.5%) had a follow-up histopathological diagnosis of cervical intra-epithelial neoplasia (CIN) 2/3. Only 4 of 107 patients with HPV-negative LSIL (3.7%) had CIN 2/3. Conclusions: In the largest study to date to document histopathological follow-up of older women with LSIL and HPV test results, no histopathological CIN 2/3 diagnoses were identified in women 50 years and older with HPV-negative LSIL. HPV test results stratified women with LSIL cytology findings into lower- and higher-risk groups for follow-up histopathologic CIN 2/3 outcomes.