To compare clinical pregnancy rate (PR) and live birth rate (LBR) between Endometrin monotherapy versus Endometrin and P in oil combination therapy in assisted reproductive technology (ART) cycles.Retrospective analysis.Large private practice.Patients undergoing autologous fresh IVF cycles, autologous frozen ET cycles, and fresh oocyte donor cycles were included for analysis.Endometrin as a single agent for luteal support, Endometrin monotherapy or Endometrin with P in oil used at least once every 3 days for luteal support, Endometrin combination therapy.Clinical PR and LBR.A total of 1,034 ART cycles were analyzed. Endometrin monotherapy was used in 694 of 1,034 (67%) cycles and Endometrin combination therapy was used in 340 of 1,034 (33%) cycles. In all fresh cycles, clinical PR was not significantly different (IVF autologous: Endometrin monotherapy 46.9% vs. Endometrin combination therapy 55.6%; donor oocyte endometrin monotherapy 45.2% vs. Endometrin combination therapy 52.0%). Frozen ET cycles had a significantly higher clinical PR and LBR with combination therapy group compared with monotherapy (clinical PR 47.9% vs. 23.5%; LBR 37.5% vs. 17.3%).Endometrin monotherapy was sufficient for the P component of luteal support and provided high PRs for fresh cycles in both autologous and donor oocyte cycles. Clinical PR and LBR in frozen ET cycles were significantly improved with the addition of IM P to Endometrin therapy. This may reflect the fact that lesser quality embryos are transferred in frozen ET cycles, and more intense P support is required for comparable PRs.