Context: Conjugal artificial insemination (CAI) is commonly the first therapeutic approach in cases of infertility. Due to the limited success of this method, a significant amount of patients end up requiring more complex treatments, namely IVF or ICSI. In order to improve the effectiveness of the clinical management and achieving higher success rates, optimizing resources, time and limiting the frustration generated by the failed attempts, the development of prognostic markers of success is vital. Single-stranded spermatic DNA fragmentation (ssSDF) has been described as a limitating factor in fertility. Objective: The aim of this study consisted in establishing the negative predictive value of the ssSDF in CAI cycles and find a threshold over which we would not recommend to undergo to this treatment. Methods: Prospective and double blind study. Patients: 90 couples who did 188 CAI cycles from the Hospital Parc Taulí. Intervention: Single-stranded spermatic DNA fragmentation was determined by the alkaline Comet assay in a fraction of the semen sample used for treatment. Main outcome results: No pregnancies were reported in cases of ssSDF above 60%. Results: 19 pregnancies were obtained, with a cumulative rate of 21,1%. Retrospectively, if this hypothetical cut-off value had been applied, a 18.4% increase in the pregnancy rate would have been observed. Conclusions: The assessment of single-stranded spermatic DNA fragmentation by the alkaline Comet assay allows an enhanced patient selection for intra-uterine insemination. More data are mandatory in order to prospectively confirm the presented model and hopefully provide better counseling to couples seeking the more adequate assisted reproductive technology.