The diagnosis of Fitz-Hugh-Curtis syndrome (FHC) is often missed or delayed in patients with right upper quadrant pain (RUQ). To develop a decision rule that predicts FHC in females with RUQ pain based on a constellation of historical features, physical examination findings and laboratory results. We conducted a prospective study to test the utility of our FHC decision rule in sexually active females, aged 13-20years, with RUQ pain who were seen in an urban ED over 57months. The decision rule was based on 4 features: 1. Presence of pleuritic chest pain, 2. Tenderness over the anterior border of liver, 3. History of worsening pain on R lateral position and 4. An erythrocyte sedimentation rate>30mm/h. The rule was considered positive if all 4 features were present. FHC was diagnosed in patients with RUQ pain and a positive GEN-PROBE Aptima Combo Assay for either gonorrhea or chlamydia on urine or endocervical specimens. 130 patients were enrolled. 24 were excluded, leaving 106 (81.5%) for analysis. 34/106 (32%) had STI/FHC. There were no differences in mean age or sexual characteristics between those with and without STI/FHC. A positive FHC decision rule had a positive predictive value of 75% (95%CI: 46.8%-91.1%) based on 96 cases for whom all features were available for analysis. Our decision rule shows promise in allowing for the early identification of FHC in adolescent and young adult females. Additional study is needed to corroborate these findings and test its generalizability.