Visualizing single-cell dynamics shaping complex tissues and understanding the underlying mechanisms is an overarching goal in biology. However, these complex biological phenomena often cross large spatiotemporal scales, as multicellular systems can grow over the course of days. Furthermore, biological processes and especially in vitro models are often affected by sample-to-sample heterogeneity. A microscope for live imaging of such systems must provide high throughput within each experiment to draw robust conclusions. Additionally, it must provide sufficient spatiotemporal resolution and image quality for large light-scattering samples while minimizing light dosage and keeping the sample accessible. Here we present an open-top, dual-view and dual-illumination light-sheet microscope, combining the advantages of multi-view imaging with an open-top geometry and a multi-well sample holder enabling long-term multi-position three-dimensional (3D) live imaging of large specimens.