Skeletal muscles possess the combinational properties of high fatigue resistance (1,000 J/m 2 ), high strength (1 MPa), low Young's modulus (100 kPa), and high water content (70 to 80 wt %), which have not been achieved in synthetic hydrogels. The muscle-like properties are highly desirable for hydrogels' nascent applications in load-bearing artificial tissues and soft devices. Here, we propose a strategy of mechanical training to achieve the aligned nanofibrillar architectures of skeletal muscles in synthetic hydrogels, resulting in the combinational muscle-like properties. These properties are obtained through the training-induced alignment of nanofibrils, without additional chemical modifications or additives. In situ confocal microscopy of the hydrogels' fracturing processes reveals that the fatigue resistance results from the crack pinning by the aligned nanofibrils, which require much higher energy to fracture than the corresponding amorphous polymer chains. This strategy is particularly applicable for 3D-printed microstructures of hydrogels, in which we can achieve isotropically fatigue-resistant, strong yet compliant properties.polyvinyl alcohol | anti-fatigue-fracture | freeze−thaw | prestretch | 3D printing B iological load-bearing tissues such as skeletal muscles commonly show J-shaped stress−strain behaviors with low Young's modulus and high strength on the order of 100 kPa and 1 MPa, respectively (1, 2). Moreover, despite their high water content of around 75 wt % (3), skeletal muscles can sustain a high stress of 1 MPa over 1 million cycles per year, with a fatigue resistance over 1,000 J/m 2 (4). The combinational properties of skeletal muscles (i.e., high fatigue resistance, high strength, superior compliance, and high water content) are highly desirable for hydrogels' nascent applications in soft biological devices, such as load-bearing artificial tissues (5), hydrogel bioelectronics (6-9), hydrogel optical fibers (10, 11), ingestible hydrogel devices (12), robust hydrogel coatings on medical devices (13-17), and hydrogel soft robots (18)(19)(20).Although various molecular and macromolecular engineering approaches have replicated parts of biological muscles' characteristics, none of them can synergistically replicate all these attributes in one single material system (SI Appendix, Table S1). For example, both strain-stiffening hydrogels (21, 22) and bottle brush polymer networks (1, 23) can mimic the J-shaped stress− strain behaviors, but their fracture toughness is still much lower than biological tissues, since no significant mechanical dissipation has been introduced in these materials for toughness enhancement. Although various tough hydrogels (24-26) have been developed by incorporating various dissipation mechanisms, they are susceptible to fatigue fracture under repeated mechanical loads, since the resistance to fatigue crack propagation after prolonged repeated mechanical loads is the energy required to fracture a single layer of polymer chains, unaffected by the additional dissipation (2...