The company's Spirit of Britain ferry departed Dover just after 23:00 BST on Tuesday.
The first P&O ferry has crossed the English Channel since the company sparked outrage by sacking 800 workers without notice last month.
The operator confirmed that the Sprit of Britain will initially carry only freight and no tourist traffic.P&O said the incident was caused by a "temporary mechanical issue" that had been resolved. The Sprit of Britain had been held in port by the Maritime and Coastguard Agency since 12 April due to a number of unspecified deficiencies, but was cleared to sail again on Friday.
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