The tissue repair field has made great strides in understanding how division of stem cells can restore injured organs. However, emerging evidence suggests many tissues rely on non-stem cell mechanisms to restore tissue mass after injury. Polyploidy can restore tissue mass by increasing cell size (hypertrophy). In addition to our work on the Drosophila hindgut, injuring the adult Drosophila abdominal and ovarian follicle epithelia causes polyploidization/hypertrophy. 30% resection of the liver, arguably the most highly regenerative mammalian organ, results in full tissue mass restoration exclusively by hypertrophy. Further, blocking liver mitosis leads to full regeneration of 66% of resected liver mass by hypertrophy. A developmental switch from injury-induced cell division to cell hypertrophy also occurs during normal heart development and classic studies found ploidy increases during hypertrophy of repairing kidneys. Importantly, liver and heart hypertrophy can involve multiple S-phases without division, called endocycles, the same mechanism used in the injured fly hindgut. Despite its conserved use, the reasons for hypertrophy instead of division are unclear. Thus, our work has potential to substantially improve our understanding of overlooked yet conserved tissue repair mechanisms.