Adhesion and proliferation of vascular endothelial cells are important parameters in the endothelialization of biomedical devices for vascular applications. Endothelialization is a complex process affected by endothelial cells and their interaction with the extracellular microenvironment. Although numerous approaches are taken to study the influence of the external environment, a systematic investigation of the impact of an engineered microenvironment on endothelial cell processes is needed. This study aims to investigate the influence of topography, initial cell seeding density, and collagen coating on human umbilical vein endothelial cells (HUVECs). Utilizing the MultiARChitecture (MARC) chamber, the effects of various topographies on HUVECs are identified, and those with more prominent effects were further evaluated individually using the MARC plate. Endothelial cell marker expression and monocyte adhesion assay are examined on the HUVEC monolayer. HUVECs on 1.8 μm convex and concave microlens topographies demonstrate the lowest cell adhesion and proliferation, regardless of initial cell seeding density and collagen I coating, and the HUVEC monolayer on the microlens shows the lowest monocyte adhesion. This property of lens topographies would potentially be a useful parameter in designing vascular biomedical devices. The MARC chamber and MARC plate show a great potential for faster and easy pattern identification for various cellular processes.