Background: The term "threatened abortion" refers to a clinically descriptive condition in which women who are less than 20 weeks pregnant experience cervical closure, vaginal spotting or bleeding, and maybe moderate uterine cramping. Ultrasonography and maternal serum cancer antigen-125 (CA-125) appear to be useful biomarkers for early pregnancy outcome prediction in cases of impending miscarriage. Objectives: This work aimed to study the role of serum CA-125 and Ultrasound in early prediction of outcome of threatened abortion. Patients and methods: This case control study was conducted in El- Menoufia University Hospital and El- Warak General Hospital from February 2021 to March 2022. Full history taking, obstetric history, menstrual history, ultrasonography, and serum CA-125 measurements were done for all studied women. Results: Significant area under curve with cutoff > 29 IU/ml showed that CA-125 had a very high reliability of differentiation between the complete abortion group and the control group, aborted cases were highly significant as regards high CA-125 (P=0.000). Multivariate analysis revealed that the most significant predictors of threatened abortion were yolk sac diameter (YSD), followed by CA1-25, with OR (95%), p-value [5.014 (1.985-8.068)], p-value < 0.001; [3.712 (2.056-6.446), p-value 0.027], while the rest had insignificant predictors of threatened abortion, with p-value (p > 0.05). Conclusions: The use of CA-125 and ultrasound in the first trimester represents a non-invasive, early, and rapid procedure that may be regarded as a good predictor of the outcome of pregnancy in instances with threatening abortion with cut off level more than 29 IU/ML of CA-125.