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STUDY OBJECTIVE To evaluate the clinical parameters of hospitalized patients presenting with pelvic inflammatory disease (PID) for the presence of tubo-ovarian abscess (TOA) and predict the need for intervention. DESIGN A prospective cohort study. SETTING A tertiary care university medical center. PATIENTS Ninety-four patients were diagnosed with complicated PID and hospitalized between 2015 and 2017. INTERVENTION Patients with PID were treated with parenteral antibiotics according to Centers for Disease Control guidelines. Demographic, clinical, sonographic and laboratory data for patients with PID were analyzed. Inflammatory markers including C-reactive protein (CRP), white blood cells (WBCs), erythrocyte sedimentation rate (ESR), and clinical parameters were collected at admission and during hospitalization. MEASUREMENTS AND MAIN RESULTS Forty-eight (51.1%) of 94 patients hospitalized with complicated PID were diagnosed with TOA sonographically. C-reactive protein levels were the strongest predictor of TOA, followed by WBC count, ESR, and fever on admission. The area under the receiver operating characteristic (ROC) curve for CRP, WBC, ESR, and fever was 0.92, 0.75, 0.73 and 0.62, respectively. C-reactive protein specificity was 93.4% and sensitivity was 85.4% for predicting TOA, with cut-off value of 49.3 mg/L. Twelve patients (25%) failed conservative management and underwent surgical intervention including laparoscopy (n = 7), CT-guided drainage (n = 4), and laparotomy (n = 1). In this group, CRP levels significantly increased from admission to day 1 and day 2 during hospitalization (128.26, 173.75, and 214.66 mg/L, respectively; p < .05 for both). In the conservative management group, CRP levels showed a plateau from admission to day 1 and then a decrease until day 3 (110, 120.49, 97.52, and 78.45 mg/L, respectively). CONCLUSIONS C-reactive protein is a sensitive, specific inflammatory marker for predicting TOA in patients with complicated PID, and levels >49.3 mg/L suggest the presence of TOA. In the TOA group, CRP level trends correlated well with success or failure of conservative management. Increasing CRP levels during treatment may be used as an indicator of the need for invasive intervention, and daily CRP measurements can help predict the need for invasive intervention.