High-density polyethylene (HDPE) pipe has many advantages such as good flexibility, corrosion resistance, and long service life. It has been introduced into nuclear power plants for transportation of cooling water in U.S. and Europe. Recently, four HDPE pipelines (PE4710) were used in essential cooling water system with operating pressure of 0.6 MPa and operating temperature of no more than 60 °C in a newly established AP1000 nuclear power plant in Zhejiang, China. The outside diameter and thickness are 30 in. and 3.3 in., respectively, which are much larger and thicker than traditional HDPE pipe for natural gas. This brought forward a challenge for nondestructive testing (NDT) and safety assessment of such pipes. In this paper, a solution for inspecting electrofusion (EF) joints of thick-walled HDPE pipes is presented, and the results of an on-site inspection of the nuclear power plant are revealed. To expand the thickness up-limit of previously developed ultrasonic-phased array instrument, an optimization method was proposed by calculating weighing effects of different testing parameters and introducing the concept of overall performance according to practical requirement, by comprehensively considering sensitivity, penetration, signal-to-noise ratio (SNR), resolution, and accuracy. Typical defects were found in field inspection. The result shows that the presented technique is capable of inspecting EF joints for connecting large-size HDPE pipes used in nuclear power plants.