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Abstract Long-term pituitary down-regulation with a gonadotrophin-releasing hormone (GnRH) agonist for 3–6 months prior to IVF/intracytoplasmic sperm injection (ICSI) improves clinical pregnancy rates in endometriosis patients. However, some discussion about this treatment strategy still exists. This retrospective study from a tertiary-care university hospital examined the efficacy and safety of IVF/ICSI with and without long-term pituitary down-regulation in severe endometriosis patients (surgically confirmed American Society for Reproductive Medicine stages III and IV). All first IVF/ICSI treatment cycles between January 2009 and January 2012 were analysed. In patients treated with ( n = 68) and without ( n = 45) long-term pituitary down-regulation, 13 (19.1%) versus nine (20.0%) ongoing pregnancies after fresh embryo transfer (adjusted OR 0.58, 95% CI 0.18–1.86,) and 24 (35.3%) versus 10 (22.2%) ongoing pregnancies after fresh and cryopreserved embryo transfers (adjusted OR 1.62, 95% CI 0.60–4.38) were accomplished, respectively. Three complications (2.7%) and three recurrences (2.7%) were reported, only in patients treated with long-term pituitary down-regulation. The 1-year cumulative endometriosis recurrence rate was 7.3%. IVF/ICSI in patients with severe endometriosis is safe with low complication and recurrence rates. A favourable effect, albeit non-significant, of long-term pituitary down-regulation in achieving an ongoing pregnancy was observed only after including cryopreserved embryo transfers. Long-term pituitary down-regulation with a GnRH agonist for 3–6 months prior to IVF or intracytoplasmic sperm injection (ICSI) improves pregnancy rates in endometriosis patients. However, some discussion about this treatment strategy still exists. This retrospective study examined the efficacy and safety of IVF/ICSI with and without long-term pituitary down-regulation in severe endometriosis patients. All first IVF/ICSI treatment cycles between January 2009 and January 2012 were analysed. In patients treated with long-term pituitary down-regulation ( n = 68) 13 (19.1%) ongoing pregnancies were accomplished after fresh embryo transfer and 24 (35.3%) after fresh including frozen embryo transfers. In patients treated without long-term pituitary down-regulation ( n = 45), nine (20%) ongoing pregnancies were accomplished after fresh embryo transfer and 10 (22.2%) after fresh including frozen embryo transfers. Three complications (2.7%) and three recurrences (2.7%) were reported, only in patients treated with long-term pituitary down-regulation. This study showed that IVF/ICSI in patients with severe endometriosis is a safe procedure with low complication and recurrence rates. Long-term pituitary down-regulation with a GnRH agonist is more beneficial in achieving an ongoing pregnancy after including frozen embryo transfer cycles.