Purpose: To determine the role of HE 4 in diagnosing ovarian cancer in preoperative adnexal masses and to compare it with CA 125 and RMI.Methods: It was a cross sectional study conducted in the department of Obs and Gynae and 88 women with adnexal masses who were planned for surgery were recruited from the Gynaecology OPD. They underwent history taking, examination, ultrasound and routine PAC investigations including serum CA 125 and HE 4 measurement. RMI and ROMA score were calculated using standard formula. All the patients underwent surgery and based on histopathology they were divided into benign and malignant groups. The tumor marker levels in the two groups were compared using the Mann–Whitney U test.Results: Median value of CA125 and HE 4 in malignant group was higher as compared to benign group i.e. 44.33 U/ml vs 19.9 U/ml, p = 0.014 and 44.92 pmol/l vs 20.9 pmol/l, p = 0.048 respectively. On comparing all the tumour markers and their combinations, highest PPV (88.9%) with acceptable NPV (80.7%) was found with ROMA followed by HE4 (PPV 85.7% and NPV 77.97%) and RMI (PPV 76.92% and NPV 83%). CA125 has lowest PPV (52%) but comparable NPV (80.85%)Conclusion: HE 4 can be used for preoperative detection of ovarian tumors with predictive accuracy better than RMI and CA 125 and is surpassed only by ROMA for the same.