Abstract: The current temporary plugging tests are unable to meet the requirements of high temperature, high pressure, and large-scale conditions,providing insufficient operational guidance for perforation temporary plugging. To address these issues, a large-scale high-pressure bearing temporary plugging experimental device for perforation was designed, which considered the influence of spherical segment diameters of the knot-type temporary plugging agent, reservoir temperature, and fluid pressure,etc. Through perforation plugging experiments, the law of temporary plugging was revealed, and the relationship between the perforation diameter and the knot size, as well as the influence of temperature and pressure on the plugging effect were clarified. The results demonstrate that optimal sealing of 12 mm perforations requires knot-type plugging agents with spherical segment diameters of 15–22 mm, whereas 10 mm perforations necessitate agents with 13–14 mm diameters. Crucially, the plugging agent diameter should exceed the perforation size by 3–5 mm to ensure effective plugging. The knot-type plugging agent can effectively plug the breakdown disk and sliding sleeve and can maintain effective plugging under the pressure of 25 MPa, and sustain effective plugging for 5–7 days at 20 MPa and 40–95 °C. The findings of the experimaental results suggest that strategically deploying properly sized knot-type plugging agents can block advantage of liquid inlet perforation holes, thereby enhancing uniform fracture initiation and propagation among multiple clusters within a stimulation stage. This research provides foundational insights for optimizing field-scale temporary plugging strategies.