A cohort follow-up study was designed to compare the efficacy of IVF using frozen donor semen (IVF-D) following previously failed DI cycles (unexplained female infertility) and direct IVF-D treatment because of tubal infertility (control group). The cohort comprised 189 couples initiating IVF-D after previously failed DI cycles (n = 126) or directly (n = 63). Couples were followed until completion (success or drop-out for personal or medical reasons). Live births and drop-out were expressed both as rate per cycle and crude cumulative rate. Characteristics of IVF-D cycles were similar between the two groups. Moreover, overall outcome was also similar in terms of crude cumulative live birth rate (54.0 versus 57.1% for failed DI cycles and tubal infertility groups respectively). This is the first report on crude cumulative live birth rate based on a cohort follow-up study in unexplained previously failed DI cycles and tubal infertility. Previously failed DI cycles did not impair the chances of achieving a successful pregnancy using IVF-D in this series. Slight oocyte dysfunction, which might underlie the failure of DI cycles, might be overcome using IVF-D.