Chlamydia trachomatis is a significant etiologic agent responsible for pelvic inflammatory disease leading to tubal infertility. A screening test aimed at identifying women at risk for Chlamydia trachomatis would be of great utility. The Papanicolaou smear is the most widely used screening test in the world. The association of inflammatory cells in the Papanicolaou smear to Chlamydia infection is controversial. We retrospectively examined the Papanicolaou smears of 80 Chlamydia-negative patients with 80 age-matched Chlamydia-positive patients in a high-risk population to see if a significant difference in inflammation was noted between the two groups. We found a statistically significant difference in inflammation scores between the Chlamydia-positive and Chlamydia-negative groups, evidenced by a sensitivity of 83% and a positive predictive value of 65% when using inflammation on Papanicolaou smears as a marker for Chlamydia infection. Grading of inflammation in the Papanicolaou smear can be of potential use in defining patients at highest risk for Chlamydia in a group considered to be at high risk based on sexual history.