The aim of the present randomized, comparative study was to evaluate the effect of reduced culture volumes on sibling human embryo development.Firstly, sibling injected oocytes obtained from 88 out of 165 consenting couples undergoing infertility treatment were cultured either in large (35 μl) or in small drops (15 μl) of culture medium. Secondly, sibling injected oocytes from 77 couples were cultured either in large (35 μl) or in mini drops (7 μl). Embryo quality on day-2 and day-3 and blastocyst formation rate on day-5 were evaluated.No statistically significant difference in terms of embryo quality was detected comparing embryos cultured either in large (35 μl) or small (15 μl) drops until blastocyst stage. Similarly, no difference appeared between large (35 μl) or mini (7 μl) drops until day-3, however a significantly higher blastocyst formation rate was observed in mini (7 μl) drops on day-5.Reduced culture volume seems not to influence early embryo development but a reduction of medium appears to positively affect blastocyst development. This supports the hypothesis that the pre-implantation embryo produces autocrine factors which exert a positive effect on embryo development when culture is performed in a reduced volume.