The 31-year-old had not played for French club Brive since March due to shoulder and elbow problems, and an off-season operation on the former has not had the desired effect, leaving him with no option but to hang up his boots on medical advice.
Popham won 33 caps for his country, the most recent of which was the victory over England at Twickenham in 2008, and also played in the 2003 and 2007 World Cups.
At club level he started out with Newport and went on to play for Leeds and the Scarlets before making the move across the channel to Brive in 2008.
"We have been talking to a few different clubs and I have been waiting to see what the surgeon had to say," he said.
"It's incredibly disappointing, but the advice is that my playing days are over and I have to accept what the experts say.
"I'm currently assessing my options, but I would love to stay in rugby and I'm going to get involved with Newbridge youth and do my coaching badges and take it from there.
"The game has given me so much, I've been all over the world and had lots of amazing experiences and memories to look back on and have also made some great friends.
"It's a sad day to realise it's the end of a chapter for me, but it also makes me extremely happy to reflect on the experiences and achievements I've been lucky enough to take in during my rugby career."
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