Aims: Debate over the optimal timing of oocyte denudation following oocyte retrieval continues. Multinucleation has been associated with lower embryo quality and implantation rate. Defining oocyte characteristics might increase the chances of better embryo selection. This study aimed to investigate the laboratory and clinical outcomes of intracytoplasmic sperm injection when the oocytes were denuded immediately after oocyte retrieval. Methods: A prospective randomized sibling-oocyte study was performed. The participants were under 40 years of age with more than 5 oocytes. Patients with male factors were excluded. The study and control groups were formed by simple randomization. The study group underwent oocyte denudation immediately. In the control group, oocytes were routinely incubated in an equilibration solution for 2 h until the removal of the cumulus cells. Outcome measures were normal fertilization (two pronuclei, 2PN), multinucleation rate, the proportion of good quality embryos, blastocyst formation, and pregnancy rate. Results: A total of 792 oocytes were collected from 54 participants (mean age: 30.6±3.7 years). The fertilization rate was higher in the study group (n=209 in 376) compared with the controls (n=201 in 416) (55.6% vs. 48.3%, p=0.041). The multinucleation rate (6.6% vs. 4.3%, p=0.150), proportion of grade 1 embryos on day 3 (48.7% vs. 43%, p=0.112) and day 5 (27.7% vs. 23.8%, p=0.214), the proportion of embryos reaching blastocyst stage (34.0% vs. 28.1%, p=0.072), and the pregnancy rates (78.6% vs. 71.4%, p=1.000) were similar. Conclusions: Our results demonstrated that immediate removal of cumulus cells does not have any negative impact on intracytoplasmic sperm injection outcomes.