Abstract: This retrospective cohort study investigated whether reproductive outcome could be improved in couples presenting with a high level of sperm DNA fragmentation (SDF) by treating the ejaculate with the magnetic cell sorting (MACS) sperm selection procedure in combination with prior density gradient centrifugation (DGC). Only men presenting with ≥30% sperm DNA in the ejaculate were included because these patients can be potentially treated with MACS to reduce the proportion of sperm presenting DNA damage. In total, 305 couples were included in this study, and from these, 216 women underwent autologous ICSI (AUTO-ICSI), whereas the remaining 89 participated in oocyte donor ICSI (DONOR-ICSI). Ejaculates were collected and DGC treated with and without MACS. Live birth and miscarriage rates resulting from ICSI observed after clinical pregnancy were determined. Sperm selection using DGC or a combination of DGC and MACS did not show any statistical difference with respect to live birth rate of couples undergoing either AUTO-ICSI or DONOR-ICSI, irrespective of whether the couples had a moderate (≥30 to <50%) or high (≥50%) level of SDF. Remarkably, there was no evidence of miscarriage in either cohort of patients (AUTO-ICSI or DONOR-ICSI) following the MACS procedure.