Purpose The objective of this study was to evaluate a panel of three sperm function tests; tests known to assess different aspects of sperm functionality and genomic integrity, the: 1) Sperm DNA Accelerated Decondensation (SDAD TM ) Test, 2) Sperm DNA Decondensation (SDD TM ) Test, and 3) Sperm Penetration Assay (SPA), determining if positive and negative test scores correlated with failed and successful ICSI outcomes, respectfully. Methods A prospective, double blinded, cohort study was performed. One study sample (ejaculated semen) was collected by each of the 60 male partners of the 60 couples enrolled in the study; males whose female partners were found to have no major female factor issues. The sperm from each male was analyzed in the SPA, and SDAD and SDD Tests, and used for ICSI (1 ICSI cycle per couple). Results The ICSI cycle pregnancy rate for this study was 50 %, with a delivery rate040 % (n060 ICSI cycles). The SPA and SDD Test scores did not significantly predict ICSI outcome when used as stand-alone tests (p>>0.05). However, when the SPA and SDD Test scores were used together, ICSI outcomes for a subgroup of 10 (16.7 %) males, were significantly predicted (p00.03), with 1 live birth, and 9 negatives where the transferred embryos did not implant. In total, 38.4 % of the couples in this study were found to have a very poor chance for a successful ICSI cycle. Conclusion SDAD Test scores alone, and SPA and SDD Test scores used together, significantly predicted failed ICSI outcomes. This indicates that the scores obtained when analyzing patients' sperm using a panel of sperm function tests; specifically, the SPA, and SDAD and SDD Tests, can be used to identify infertile couples who should not be directed to ICSI.