IntroductionAt present, studies comparing intrauterine insemination in the natural cycle versus intracervical insemination in the natural cycle in women undergoing artificial insemination with donor sperm are scarce.Methods and analysisWe perform a randomised controlled non-inferiority trial among five secondary and tertiary fertility clinics in the Netherlands and one tertiary fertility clinic in Belgium. Women eligible for artificial insemination with donor sperm are included. We perform six cycles of artificial insemination with donor sperm within a time horizon of 8 months comparing intrauterine insemination in the natural cycle with intracervical insemination in the natural cycle. The primary outcome is ongoing pregnancy leading to live birth conceived within eight months after randomisation. Secondary outcomes are clinical pregnancy rate, miscarriage rate, multiple pregnancy rate, pregnancy complications (preterm birth, birth weight Ethics and disseminationThe study has been approved by the Medical Ethical Committee of the Academic Medical Centre and from the Dutch Central Committee on research involving human subjects (47330-018-13). The boards of the participating hospitals approved the study. Results will be disseminated through peer-reviewed publications and presentations at international scientific meetings.Trial registration numberNCT4462