Background: Obesity remains an important risk factor for women planning for pregnancy because of its adverse effects on reproductive outcome. In individuals who experience difficulty in reducing significant weight with lifestyle intervention alone, the use of anti-obesity drugs can be an adjunct. Objective: To evaluate the efficacy of Orlistat (a pancreatic lipase inhibitor) therapy on achieving pregnancy in overweight and obese sub-fertile women. Patients and methods: This prospective study was carried out, involving 120 case of obese and overweight sub-fertile and primary infertility women that attend to antenatal care in obstetrics and gynecology clinics in both Al- Hussein Hospital and Kom-Hamada Hospital, They were divided into 2 groups: Group I: Patients received Orlistat (120 mg) twice daily for 6 months period, and Group II: Patients counseled for life style modification only. The duration of the study ranged between April 2019 and October 2020. Results: In group I with BMI less than 30, there were 9(30%) with pregnancy outcome, 5(16.7%) with pregnancy outcome with BMI more than 30. In group II with BMI less than 30, there were 2(6.9%) with pregnancy outcome, 2(6.5%) with pregnancy outcome with BMI more than 30. There was a significant difference between 2 groups as regard pregnancy outcome. Conclusion: Orlistat improved ovulation as it acted indirectly by weight reduction more than life style modification alone.