Abstract Study question Does the transfer of a single vitrified-thawed blastocyst optimise obstetric and neonatal outcomes compared to a single fresh blastocyst transfer? Summary answer A single vitrified-thawed blastocyst transfer is associated with a lower risk of preterm delivery and small-for-gestational-age babies but a higher risk of large-for-gestational-age babies. What is known already Several studies have been performed comparing the outcomes of ART pregnancies after fresh or frozen embryo transfers. Nevertheless, a closer examination of the available studies indicates a significant heterogeneity in terms of the clinical protocols they compare, predominantly in regards to the developmental stage of the embryos (cleavage vs. blastocyst), the number of embryos transferred (single vs. multiple) and the cryopreservation method used (slow-freezing vs. vitrification). The use of single blastocyst transfer and vitrification is currently considered the gold standard of care but relevant studies on the safety of these technologies regarding the obstetric and neonatal outcomes are lacking. Study design, size, duration Autologous ART cycles where a single Day 5/6 embryo was transferred were identified (n = 188,730) in the Australian ART registry (ANZARD) and these were linked with 20,214 birth records (deliveries >20 weeks of gestation or with a weight of > 400gr of the Perinatal Data Collection which had taken place in two Australian States between 1st of January of 2009 and 31st of December of 2016. Cycles including preimplantation genetic testing or assisted hatching were excluded. Participants/materials, setting, methods Two cohorts were formed, the Fresh group, containing 89,299 ART treatment cycles linked to 11,138 PDC birth records, and the Vitrified-Thawed (VT) group, containing 75,596 ART treatment cycles linked to 7,518 PDC birth records. Comparisons of obstetric and neonatal outcomes between these groups were performed using generalized estimating equations to account for the clustered nature of data while also accounting for multiple confounders. Significance level was set at 0.01 to correct for multiplicity of testing. Main results and the role of chance The risk of preterm delivery was significantly lower in the VT group compared to the fresh group (adjusted relative risk-aRR: 0.78, 99% CI 0.69-0.88). This persisted in a sensitivity analysis (accounting for the embryo ranking within each cohort) by comparing pregnancies occurring after the first vitrified-thawed embryo transfer following a freeze-all cycle (VTFA) with the fresh ET group (aRR: 0.71, 99% CI: 0.54-0.94). The probability of pregnancy-induced hypertension was not significantly different between the two groups (aRR: 1.15, 99% CI: 0.99-1.34). There was also no indication of an increased risk of PIH when the VTFA group was compared to the fresh ET group (aRR: 0.94, 99% CI: 0.68-1.30). The probability of SGA was 35% lower in the VT group compared to the fresh ET group (aRR: 0.65, 99% CI: 0.56-0.74). When only VTFA babies were compared with the fresh ET group, then the probability of SGA was 20% lower, but this was not statistically significant. For LGA babies, the risk was significantly higher (∼45%) in the VT group compared to the fresh ET group (aRR: 1.46, 99% CI: 1.30-1.65). The LGA risk remained significantly higher in the VTFA compared to the fresh ET group (aRR: 1.34, 99% CI: 1.04-1.72). Limitations, reasons for caution This is a population-based study using linked administrative datasets; therefore not all confounders could be accounted for. Furthermore, the smaller sample size of the sensitivity analysis combined with the strict level of significance adopted might have rendered some sensitivity analyses underpowered particularly for rare outcomes Wider implications of the findings This analysis shows the differences in obstetric and neonatal outcomes between fresh and frozen embryo transfers studying vitrification and single embryo transfer exclusively. For certain outcomes, it appears that the effects are modified when the embryo ranking within each cohort is accounted for. Trial registration number Not applicable