<p>High-resolution vascular imaging in zebrafish embryos offers unparalleled insight into angiogenesis, yet quantitative analysis remains limited by manual workflows and inconsistent segmentation. To overcome this, we developed VISTA-Z (Vascular Imaging and Segmentation for Topology Analysis in Zebrafish), an automated Python-based pipeline designed to standardise vascular quantification across diverse fluorescent datasets. The workflow combines adaptive contrast enhancement, vessel segmentation using Meijering filtering, artefact removal through segment labelling, and skeleton-based topology analysis with refined branchpoint detection. Metrics are normalised to physical units and imaging depth, enabling reproducible comparisons across experiments. We validated VISTA-Z using multiple endothelial transgenic lines and developmental stages. The pipeline detected subtle and severe phenotypes, including brain vessel loss in <i>foxc1a</i> mutants, brain and trunk vessel loss in <i>kdrl</i> mutants and widespread hyper-angiogenesis in <i>plxnd1</i> crispants. VISTA-Z is an open-source, scalable platform for reproducible high-throughput quantification of zebrafish vascular architecture, providing a standardised framework for developmental research and preclinical screening</p>