Introduction: Pelvic inflammatory disease (PID) refers to an infectious and inflammatory disorder of the female upper genital tract. It is common among young sexually active individuals and is a major health problem both in developed and developing countries. It is usually a polymicrobial infection; however, Chlamydia trachomatis is the commonest causative agent transmitted sexually. Pelvic inflammatory disease is diagnosed by history and clinical examination. The treatment is initially empiric. Only antibiotics are good in treatment for PID and “antibiotics with prebiotics” are a new promising treatment mode for the same. This comparative study aimed to measure efficiency and compliance of only antibiotics vs antibiotics with prebiotics in the treatment of mild, uncomplicated acute PID. Setting: Multispecialty Hospital Pune. Duration: 6 months. Materials and methods: A descriptive cross-sectional study was conducted in randomly selected 28 consecutive outpatients with mild uncomplicated acute PID. Comparative outcome of antibiotics and antibiotics with prebiotics in correlation with the reduction of amount, consistency, and malodor of vaginal discharge along with the reduction in fornical tenderness, compliance, and frequency of adverse drug reactions was done. Results: Among 28 cases, 14 (50%) were treated with oral antibiotics and 14 (50%) with oral antibiotics with prebiotics. Comparative analysis on the reduction of amount, consistency, malodor of vaginal discharge, and reduction of fornical tenderness was significant, showing antibiotics with prebiotics more effective than antibiotics. Besides, compliance was better and there were fewer adverse drug reactions with antibiotics with prebiotics. Conclusion: Antibiotics with prebiotics have better efficiency and compliance over only antibiotics in the treatment of mild, uncomplicated, acute PID.