Objectives To investigate the endometrial effects of letrozole in PCOS women with poor endometrial response (endometrium thickness ⩽7 mm) to clomiphene citrate (CC) despite adequate ovulation, using the ultrasonographic markers of endometrial receptivity. Study design Ambidirectional cohort study. Patients and methods Sixty women with anovulatory PCOS having an endometrial thickness less than 7 mm despite adequate ovulation with CC underwent ovulation induction with Letrozole (5 mg/day from cycle day 3 to 7) for one treatment cycle. Main outcome measures: Comparison of the endometrial thickness (ET) and pattern, uterine artery and spiral artery, resistance index (RI) and pulsatility index (PI) between the current letrozole and previous CC stimulated cycles. Results In the current letrozole cycle compared with the previous CC cycles, there was significantly greater midcycle endometrial thickness (8.97 ± 1.32 vs. 5.7 ± 1.2, respectively; P < 0.05), multilayered endometrial pattern (93.33% vs. 50%, respectively; P < 0.05) and rate of detection of subendometrial blood flow. Both RI and PI of spiral arteries in the letrozole cycle (0.63 ± 0.05 and 1.12 ± 0.06, respectively) showed significantly lower impedance compared to the previous CC cycle (0.75 ± 0.09 and 1.42 ± 0.13, respectively) (P < 0.05). Pregnancy rate per cycle was 20% (12/60) in the letrozole cycle, all in women with endometrial thickness ⩾7 mm. Conclusion Letrozole is an effective second-line treatment in women with inadequate endometrial response to CC, as letrozole increased endometrial thickness trilaminar pattern and improved endometrial perfusion.