During mitosis, the directional endosome-mediated transport of cell fate determinants is one way to generate daughter cells with different destinies. In Drosophila, internalized Delta ligands and Notch receptors traffic through Sara (for Smad Anchor for Receptor Activation) endosomes. In asymmetric cell division systems, Sara endosomes segregate unequally upon division, which biases Notch signaling and dictates differential daughter cell fate assignation. Besides, Notch signaling is known to regulate cell lineage during physiological renewal of the adult Drosophila midgut. Thus, I studied whether Sara plays a role in intestinal stem cell (ISC) fate decision. Live imaging assays showed that only Sara endosomes are asymmetrically dispatched during ISC mitosis. This directional partitioning of Sara endosomes into differentiating cell indicates that ISCs divide asymmetrically. Moreover, Sara mutant midguts present an accumulation of ‘ISC-like' cells and a depletion of differentiated cells, similar to a Notch loss-of-function phenotype. Therefore, Sara controls the adult Drosophila midgut homeostasis.