Background: intra Cytoplasmic Sperm Injection (ICSI) is a reliable method for single sperm selection and injection to a large number of infertile patients.  Human oocytes are naturally surrounded by cumulus cells embedded in the intracellular matrix made primarily of   hyaluronic acid (HA), which plays a role as physiological selector for Intra-Cytoplasmic Sperm Injection (PICSI). Mature spermatozoa are able to bind to and digest HA for the best chance of reaching the oocyte and to maintain fertilization.  The intact human spermatozoa are bound to immobilize HA surrounding oocyte in vitro and this leads to reduced risk of chromosomal imbalance or chromatin diseases. Selection of spermatozoa by HA before ICSI may help to optimize the outcomes of the treatment; thus, our study aimed to compare ICSI results, based on the hyaluronic acid or traditional method for sperm selection. Setting: this study conducted at International Islamic Center for Population Studies and Research, Assisted Reproduction Unit, Al-Azhar University from January to October 2015. Patients and Methods:120 couples with male factor infertility and normal wives conducted at the Assisted Reproduction Unit in the International Islamic Center for Population Studies and Research (IICPSR), Al-Azhar University, Egypt, during the period from January to October 2015. All cases were clinically evaluated and eligible for analysis by using inclusion and exclusion criteria. All studied men subjected to ejaculated sperm prepared by traditional method and another prepared by PICSI method. ICSI performed simultaneously for different oocytes from the same woman   using an ejaculated sperm by two methods from the same husband. ICSI outcomes compared to the two sequential attempts performed, respectively. Number and quality of oocytes, fertilization rates, rate of embryo cleavage and pregnancy outcomes were recorded. The collected data were tabulated and statistically analyzed.  Results: the present study showed a significant increase in the incidence of fertilization rate, the percentage of embryos with top grade in teratozoospermia and thawed semen groups with PICSI technique compared to the traditional method of ICSI groups. Finally, the percentage of pregnancy rate an increase in all groups manipulated with PICSI technique and this increase was statistically significant. Conclusion: this study shed more light on the physiological sperm selection method (PICSI) which may improve fertilization and pregnancy rates compared to the traditional selected sperm in ICSI. It is concluded that PICSI technique in Assisted Reproductive Technology (ART) is one of the very important technique that improve fertilization in case of low fertilization rate after ICSI.