"Macdonough"s second Mediterranean deployment, 10 July to 22 December 1964, was followed by a 6-month overhaul at the Charleston Naval Shipyard. Coastal operations out of home port occupied the frigate until mid-September 1965, when she proceeded to the Atlantic Fleet Missile Range and then to Guantánamo Bay, Cuba, for training exercises. Having returned to her Charleston home port in early November, "Macdonough" prepared for another Mediterranean deployment, departing Charleston at the end of the month. "Macdonough" served as flagship for the recovery effort of the Palomares Incident during the third Mediterranean deployment.