In 1927, she was sunk by being accidentally rammed by a United States Coast Guard destroyer with the loss of all hands but was raised and restored to service until stricken in 1936.

S-4 operated out of the Cavite Naval Station, with occasional visits to Chinese ports, until late 1924, when the two divisions were reassigned to the West Coast of the United States.

She departed Mare Island on 10 February 1927 and sailed to the Panama Canal Zone, where she operated through March–April, then proceeded to New London, Connecticut, arriving on 3 May.

On 17 December 1927, while surfacing from a submerged run over the measured-mile off Provincetown, Massachusetts, she was accidentally rammed and sunk by the United States Coast Guard destroyer Paulding on Rum Patrol.

Several of the salvage divers, including Eadie and previous Medal of Honor recipient Frank W. Crilley, were awarded the Navy Cross for their actions during the operation.

Another Medal of Honor recipient, Chief Boatswain George Cregan, received the Navy Cross for his service as commander of the tugboat Sagamore during the rescue attempt.

Media related to USS S-4 (SS-109) at Wikimedia Commons List of submarine classes of the United States Navy