The aim of the present study was to evaluate the role of melatonin supplementation on the main IVF outcomes in aged patients underwent IVF. 358 infertile women aged over 40 underwent a shortdown-regulation protocol and were randomized into two groups: 178 patients who received 5mg melatonin (group A) and 180 patients who did not received melatonin (group B). Oxidative stress values, mature oocytes, embryo quality, pregnancy rates and implantation rates, intrafollicular concentration of melatonin and progesterone were measured.There were significant statistical differences comparing group A with group B in terms of mature oocytes (48.2% vs 35.0%), oxidative stress (CARR U) (190 ± 41 vs 388 ± 64), antioxidative capacity (AOCs) (1,76±0,4 vs 0,89 ± 0,2), progesterone concentration in follicular fluid (10,4±1.1 ml vs 4,3±0,8 ml) and grade I embryos (45,7% vs 30,4%, p=0.0045).Melatonin intrafollicular concentrations were significantly increased after melatonin treatment (213±35 pg/ml versus 69 ± 23 pg/ml). In conclusion melatonin supplementations during ovarian stimulationin aged patients improve oocyte and embryo quality, increasing progesterone production and scavenging free radicals. Furthermorewe demonstrated that exogenous administrated melatonin is able to accumulate efficiently in the follicular fluid.