Objective: To evaluate the results of a novel protocol that allows to rescue IVF unfertilized oocytes by intracytoplasmic sperm injection (ICSI). Design: Prospective clinical trial. Setting: Private reproductive medical center. Patient(s): Thirty patients undergoing IVF. Intervention(s): Controlled ovarian stimulation (COS), conventional IVF, rescue ICSI, embryo culture, and embryo transfer. Main Outcome Measure(s): Identification of unfertilized IVF oocytes 6 hours after insemination and fertilization, and developmental rates of those oocytes after rescue microinjection, as well implantation and pregnancy rates (PR). Result(s): All oocytes (392) from 30 patients were inseminated with standard IVF 3 hours after ovum pick-up. Polar body (PB) status was checked at decumulation and rechecked 3 hours later. Eighty-two oocytes were fertilized after IVF alone and 184 nonactivated oocytes (failed fertilization) were rescue microinjected and 166 of them fertilized (20 patients). Cleavage stage on day 2 was significantly more advanced and embryo grade was higher after standard IVF fertilization than after rescue ICSI. Eight of the 30 embryos transferred were implanted in the IVF-only patients (27%) and 8 of 68 embryos in the rescue ICSI patients (12%). Conclusion(s): Rescue ICSI of unfertilized IVF oocytes 6 hours after insemination (9 hours after egg retrieval) can provide normal fertilization, embryo development, and pregnancy; however, corresponding outcome parameters tend to be impaired in comparison to the standard IVF fertilization results. [Copyright &y& Elsevier]