Background: Infertility is the inability of a married couple to conceive within one year in spite of regular marital life. Globally 10-15% of the married couples are experiencing this problem. CC is non-steroidal selective estrogen receptor modulator (SERM), has both estrogen agonist and antagonist properties. It binds to estrogen receptors primarily in the hypothalamus, which interrupts the negative feedback of the increasing estrogen level and results in continued production of FSH, which stimulates follicular growth and maturation. Its anti-estrogenic effect causes long standing estrogen receptor depletion due to its long half life (2 weeks), so it has adverse effects on the quality and quantity of cervical mucus and negative impact on endometrial development causing its thinning, implantation failure and decreased blood flow during the peri-implantation stage. Objectives: The aim of the study is to compare the effect of the following 3 drugs during induction of ovulation: 1- Clomiphene citrate, 2- Tamoxifen, 3- Letrozole. Patients and Methods: This study was carried out in El Entag El Harby Hospital. The patients were recruited from the Infertility outpatient clinic between December 2017 and June 2018. This prospective study included 150 infertile women who were diagnosed as anovulatory infertility and meet the inclusion criteria. This study followed the ethical committee rules of Obstetrics & Gynecology department, Al Azhar University. For all women with anovulatory infertility in this study; explanation of the study procedures was done to all women sharing in the study and informed written consents were obtained. In the current study, patients were divided into three groups, each group formed of 50 patients: Group 1 (CC), Group 2 (letrozole), Group 3 (TMX). First of all, the groups in our study were matched as regard to age, BMI, type and duration of infertility. Results: The current study shows a statistically significant difference between the three groups regarding the endometrial thickness, which was significantly thinner in group 1 (CC) than the other two groups; group 2 (letrozole) and group 3. Conclusion: Clomiphene citrate has a negative effect on endometrial thickness which is mostly attributed to its antiestrogenic effect. A triple layered endometrium (trilaminar pattern) is associated with higher pregnancy rates; therefore, patients receiving CC with non trilaminar pattern have reduced pregnancy rates.