© 2021 Informa UK Limited, trading as Taylor & Francis Group.The present retrospective cohort study analysed data of couples with unexplained infertility who underwent two to three intrauterine insemination (IUI) cycles. The inclusion criteria were age 20–40 years, failure to conceive for at least two years of unprotected intercourse, ovulation, normal semen analysis, and tubal patency. Total of 578 IUI cycles of 286 couples with unexplained infertility were included in the final analyses. The mean age and duration of infertility of the study population were 28.8 ± 5.1 and 5.2 ± 3.4 years, respectively. The clinical pregnancy rate (CPR) and live birth rate (LBR) per cycle were 16.6 and 13.1%, respectively. The cumulative CPR following two to three IUI cycles was 33.5% and the cumulative LBR was 26.5% for the entire cohort. The duration of infertility was significantly shorter in women whose IUI attempt were successful (p =.036). Up to three cycles of IUI with ovarian stimulation seems as an effective first-line treatment modality in unexplained infertility.IMPACT STATEMENTWhat is already known on this subject? Cont rolled ovarian stimulation combined with intrauterine insemination (IUI) is a common infertility treatment as a low-cost, less-invasive alternative to in vitro fertilisation (IVF) and was approved as a first line treatment option for unexplained infertility However, the UK National Institute for Health and Care Excellence (NICE) guideline states that IUI is not recommended to couples with unexplained infertility, male factor and mild endometriosis, unless the couples have religious, cultural or social objections to proceed with IVF. What do the results of this study add? Up to three IUI cycles with ovarian stimulation can be considered as an effective treatment modality in unexplained infertility even in couples who could not achieve pregnancy by expectant management for two years. What are the implications of these findings for clinical practice and/or further research? The clinicians should reconsider the NICE recommendation of IVF in the light of recent studies including ours which recommend IUI together when dealing couples with unexplained infertility.