Fetal vascular malperfusion (FVM) is an important pattern of placental injury. While the significance of distal villous FVM (clusters of sclerotic and/or mineralized chorionic villi) is well documented, the clinical significance of proximal (large vessel) lesions of FVM is less clear, which is the aim of this retrospective analysis. To evaluate the clinical significance and placental associations of single and co-existing categories of lesions of large vessel FVM, 24 clinical and 44 placental phenotypes of 804 consecutive placentas with at least 1 lesion of proximal vessel FVM from the 2nd half of pregnancy, divided according to the type/category of the individual FVM lesion (fetal vascular ectasia, fetal vascular thrombi, intramural fibrin deposition, stem vessel obliteration): 689, 341, 286, 267 placentas, respectively (first analysis), and single or coexisting large fetal vessel lesions: 1, 2, 3, and 4 coexisting categories of lesions: 276, 321, 162, and 45 placentas, respectively, were statistically compared (analysis of variance, Chi-square, univariate analysis). Because of multiple comparisons, p Bonferroni <0.001 was used as a threshold of statistical significance. In this population of high-risk pregnancies dominated by fetal congenital anomalies, single individual or 1-2 coexisting categories of lesions of the large vessel FVM, including fetal vascular thrombi, did not consistently correlate with clinical or placental variables and were not prognostically useful, but the coexistence of 3 or 4 lesions was associated with the most advanced gestational age, fetal congenital anomalies, distal villous FVM, particularly high grade, chorangioma/chorangiomatosis, hyper coiled umbilical cord, perivascular stem edema, and marginate/vallate placenta. Therefore, the finding of multiple lesions of the large vessel FVM not only merits a diligent search for the distal villous lesions, but also by CD34 immunostaining but justifies putting the large vessel (global) FVM on the final placental diagnosis line which in the case of up to only two lesions may not be justified.