Background: Diminished ovarian reserve (DOR) is a challenge for clinicians in IVF cycles and several treatment modalities have been suggested to improve outcomes. The aim of this study was to compare live birth rates following ovarian stimulation using a luteal phase estradiol (E2)/gonadotropin releasing hormone (GnRH) antagonist protocol (LPG group) with a letrozole/antagonist (LA group) protocol in patients with DOR. Methods: A total of 51 women with DOR, previously canceled IVF cycles and aged 40 years or less were investigated. In the LPG group (n = 26), a transdermal E2 patch was applied every other day starting 10 days after the luteinizing hormone (LH) surge. At day 11 after the LH surge, GnRH antagonists were administered for three consecutive days. In the LA group (n = 25), letrozole (5 mg/day) treatment was begun on the second day of menstruation and administered for 5 consecutive days. In both groups, gonadotropins were initiated on the second day of menstruation. Results for the two groups were compared using chi-square and Student’s t-test, as appropriate. Results: Although the initial and total gonadotropin doses were significantly higher in the LPG group, the peak E2 levels, number of oocytes and fertilization rates and cancellation rates were similar. Trends toward improved live birth rates per transfer (23% vs. 11%) and per cycle (11.5% vs. 4%) were seen in the LPG group compared to the LA group, although the differences were not statistically significant. Discussion: DOR patients with previously canceled IVF cycles may be treated with either the LPG or LA protocols.