"Agerholm" began her next deployment in January 1966 when she departed San Diego for Vietnam. There, her assigned duties included Naval Gunfire Support (NGFS), anti-submarine warfare (ASW), carrier escort, and search and rescue (SAR). In May during NGFS off the South Vietnamese coast, "Agerholm" provided call fire for a Marine Corps air spotter who was drawing heavy gunfire. The destroyer silenced the Viet Cong machine gun nest with just four rounds from her 5-inch 5"/38 caliber gun guns. On 17 June "Agerholm" aided a South Vietnamese patrol boat and took off 12 badly wounded men while on a SAR mission in the Gulf of Tonkin. The ship visited Subic Bay, Yokosuka, Kaohsiung, Hong Kong and Pearl Harbor before returning to San Diego in July. While in Yokosuka, "Angerholm" was filmed and subsequently made a cameo appearance in the 1968 movie "Nobody's Perfect".