Background: Ovarian cancer continues to pose a major challenge to physicians and radiologists. It is the third most common gynecologic malignancy and estimated to be fifth leading cancer cause of death in women, constituting 23% of all gynecological malignancies. Multi-detector computed tomography (MDCT) appears to offer an excellent modality in diagnosing ovarian cancer based on combination of its availability, meticulous technique, efficacy and familiarity of radiologists and physicians. The aim of this study was to compute sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of 64-slice MDCT in classifying ovarian masses; 95% confidence intervals were reported. Materials and Methods: We prospectively designed a cross-sectional analytical study to collect data from July 2010 to August 2011 from a tertiary care hospital in Karachi, Pakistan. A sample of 105 women aged between 15-80 years referred for 64-MDCT of abdomen and pelvis with clinical suspicion of malignant ovarian cancer, irrespective of stage of disease, were enrolled by non-probability purposive sampling. All patients who were already known cases of histologically proven ovarian carcinoma and having some contraindication to radiation or iodinated contrast media were excluded. Results: Our prospective study reports sensitivity, specificity; positive and negative predictive values with 95%CI and accuracy were computed. Kappa was calculated to report agreement among the two radiologists. For reader A, MDCT was found to have 92% (0.83, 0.97) sensitivity and 86.7% (0.68, 0.96) specificity, while PPV and NPV were 94.5% (0.86, 0.98) and 86.7% (0.63, 0.92), respectively. Accuracy reported by reader A was 90.5%. For reader B, sensitivity, specificity, PPV and NPV were 94.6% (0.86, 0.98) 90% (0.72, 0.97) 96% (0.88, 0.99) and 87.1% (0.69, 0.95) respectively. Accuracy computed by reader B was 93.3%. Excellent agreement was found between the two radiologists with a significant kappa value of 0.887. Conclusion: Based on our study results, we conclude MDCT is a reliable imaging modality in diagnosis of ovarian masses accurately with insignificant interobserver variability.