AbstractSurgical sutures are gold‐standard wound closure devices. However, they are unable to form a tight seal with surrounding tissues, raising the risks of body fluid leakage and surgical site infection. Additionally, the use of sutures can result in cracking at suture roots, damage and micro‐trauma to soft tissues due to the slicing and compression of suture fibers after their placement. Bioadhesives capable of mimicking natural biological interfaces are appealing alternatives, but they cannot achieve the same level of strength as conventional surgical sutures. Here, a tough adhesive puncture sealing (TAPS) suture, featuring swelling‐triggered bioadhesion to mend the gap between the suture and the surrounding tissues with a soft yet tough adhesive interface is reported. This unique design principle of TAPS sutures is applicable to diverse soft tissues of various defect sizes and can be controlled by modulating the hydrogel swelling kinetics. The advantages of the TAPS sutures for meniscal tear repair and intestine tissue sealing ex vivo, corroborates their favorable applications in managing mechanically active musculoskeletal and gastrointestinal tissues are demonstrated. The design and performance of the TAPS sutures offer extensive possibilities for redesigning surgical tools and developing next‐generation medical devices for wound management and tissue repair.