Urban vitality, understood as a key factor in the achievement of cities’ sustainability, shows a strong relationship with urban morphology. The city theorist Jane Jacobs suggested morphological aspects to promote vital cities in the 1960s, which remain valid in the present. However, few studies in the Andean region quantitatively exemplify this. This paper aims to test the measurement of urban vitality in a neighborhood of Quito, Ecuador, called La Mariscal, integrating Jacobs’ approach. In particular, three urban vitality indexes are evaluated with the application of GIS software using cadastral data obtained from the Metropolitan District of Quito and field data collection. Results show that context-based previous knowledge and scale of analysis are essential factors in the configuration of dimensions, indicators, and spatial representation of any urban vitality index. In the study area, land use mixture, contact opportunity, and accessibility dimensions are fundamental. Regarding indicators, the incorporation of informal small-scale commerce, the quality of sidewalks, and well-conditioned street furniture is recommended. Finally, a hybrid representation (raster and vectorial) is suggested to precisely measure urban vitality at a block scale. Altogether, by providing a comparative approach, we intend to provide a useful framework for researchers and planners to study urban vitality in Andean cities.