Objectives: It has been reported that fertilization failure is common in patients with unexplained infertility undergoing conventional in-vitro fertilization (IVF). In this study we compared fertilization rates with IVF or intracytoplasmic sperm injection (ICSI) in sibling oocytes of patients with unexplained infertility. Design: Prospective randomized study. Materials and Methods: A total of 85 patients with unexplained infertility were evaluated. We included couples with normal semen parameters (ie. count, motility and morphology) and with at least 8 oocytes retrieved. Oocytes were randomly divided into two groups; conventional IVF was performed in group I while intracytoplasmic sperm injection (ICSI) was performed in group II. Results: A total of 1458 oocytes were retrieved (mean: 17.1), IVF was performed on 726 and ICSI on 722 of them. In both groups G1 and G2 media were used for incubation of the embryos. All embryo transfer procedures were performed 3 days after oocyte retrieval. As shown in table I fertilization rates were 36.6% and 83.3% in group I and II, respectively (p<0.05). Total fertilization failure was observed in sibling oocytes of 11 couples in group I, while all these couples had embryos available for transfer from their oocytes fertilized with ICSI. Cleavage rate and embryo quality were similar between the groups. Embryo quality in 5–8 cell embryos was significantly better in ICSI group. Tabled 1IVFICSIPNo of oocytes726722No of MII oocytes540 (74.8%)Fertilization rate36.5%83.3%<0.05Cleavage rate94.5%97.8%NSDevelopmental stageG1+G2G3+G4G1+G2G3+G4≤2 cell5.6%4.0%3.7%2.6%NSNS2–4 cell19.2%13.6%22.9%22.9%NS<0.055–8 cell26.0%31.6%40.7%25.2%<0.05NS Open table in a new tab Conclusion: Our results show that fertilization rate is significantly higher when oocytes from patients with unexplained infertility are fertilized with ICSI. Serious consideration should be given to ICSI as the first option for in vitro fertilization in these patients.