To investigate an association between the presence of a giant oocyte and outcome for the cohort in in vitro fertilization (IVF). Retrospective study. Hospital-based academic medical center. IVF and IVF/intracytoplasmic sperm injection (ICSI) cycles having at least one giant oocyte (study group; n = 105), matched with cycles without a giant oocyte (external control group). A further subanalysis compared giant oocyte cycles with the next closest cycles within patients (internal control group; n = 65). Standard IVF protocols. Incidence of giant oocytes, fertilization rate, quality of cohort embryos, and pregnancy outcome. Out of 97,556 oocytes, 117 (0.12%) were giant. Compared with the external control group, cleavage in the study group was abnormal (increased percentage of 1-cell and 10-cell embryos and decreased percentage of 6-cell and 7-cell embryos), although there was no difference for percentage of embryos with perfect symmetry, fragmentation, or implantation, clinical pregnancy, or ongoing/delivered rate. The study group had two cases of pregnancy termination due to chromosomal abnormalities (4.4%) versus none in external controls. No striking differences in embryo quality existed between the study and internal control groups. A giant oocyte is associated with abnormal cleavage in cohort embryos, but not with implantation or pregnancy rates. Giant oocytes occur sporadically and appear not to reflect quality of remaining oocytes in the ovary.