With the Lions kicking off their summer tour in Hong Kong on June 1, the latest setback means the 27-year-old is all but certain to miss out on a place in Warren Gatland's squad.
"Stephen Ferris, was reviewed last week as part of his ongoing rehabilitation from an ankle injury that he sustained in November," read a statement from Ulster.
"At that review, it was discovered that although he had made excellent progress, some minor issues still remained. Those issues included function at the ankle continuing to cause pain.
"Having considered all specialist medical opinions given, Stephen underwent successful ankle surgery in Belfast yesterday, during which fragments of bone were removed.
"Stephen will be out of rugby for a further three months but following this period is expected to make a full and complete return to the game."
Ferris hade been one of the firm favourites for a starting spot let alone a squad place this summer but his season never really got going.
The ankle problem that has effectively ended his hopes and has already ruled him out of Ireland's autumn series and the recent games against Wales, England and Scotland is just the latest in a long line of injury issues to have plagued him in recent months.
Calf damage prevented him from participating in Ireland's summer tour of New Zealand and a back complaint hampered his early involvement in this season's PRO12.
Injury also scuppered his hopes of a Lions Test spot in South Africa four years ago as his knee gave out to bring his tour to a premature end.
Ferris was one of the stars of the initial weeks of the last Lions adventure, scoring tries in each of his two appearances against the Golden Lions and the Cheetahs in Johannesburg and Bloemfontein, and he had been keen to surpass that success with Britain and Ireland's elite this time around.
His likely absence is a substantial blow to Gatland and his fellow coaches, especially as fellow blindside Dan Lydiate is yet to return from ankle surgery and 2009 Test No6 Tom Croft is only gingerly making his way back from neck trouble.