To investigate the relationship between levels of circulating maternal pregnancy-associated plasma protein-A (PAPP-A) and first-trimester maternal vascular function. This was a cross-sectional study of 53 healthy, non-smoking, nulliparous pregnant women in Stockholm, Sweden. PAPP-A levels and vascular function were assessed during gestational weeks 11-14. Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Microvascular endothelial function index was calculated as peak ACh/peak SNP. Endothelium-dependent and -independent vasodilatation in the brachial artery was evaluated, respectively, by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by response to sublingual intake of glyceryl trinitrate (GTN). PAPP-A was correlated with skin microvascular endothelial function index (β = 1.008 (95% CI, 0.34-1.68), r2 = 0.17, P= 0.004). PAPP-A also correlated inversely with FMD (β = -0.052 (95% CI, -0.094 to -0.011), r2 = 0.13, P= 0.014) but did not relate to forearm endothelial function index (i.e. FMD/GTN). The results were retained in multivariate analyses including known confounding factors. First-trimester endothelium-dependent skin microvascular reactivity was positively related to PAPP-A levels. If confirmed, these novel findings suggest that first-trimester skin microvascular reactivity could be a useful early pregnancy marker of placental function. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.