Popham underwent a reconstruction to his shoulder but medical advice has concluded that the injury presents too high a risk for him to continue to play.
"We have been talking to a few different clubs and I have been waiting to see what the surgeon had to say," said the 33-times capped Newport product.
"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 take in during my rugby career.
"I remember strongly the emotions and elation of winning the Principality Cup as 22-year-old a decade ago with Newport and bringing the trophy back to Rodney Parade was one of my early highlights.
"We won the Powergen at Leeds in 2005, which was another real highlight, and then I came back to Wales with the Scarlets.
"There were some great nights at Stradey Park, but non greater than Toulouse in the Heineken Cup in 2007. They have always been one of the top clubs in Europe and we beat them home and away that year in two epic matches.
"With Wales, 'nearly' beating New Zealand in the 2003 Rugby World Cup stands out, but beating England at Twickenham for the first time in 23 years in 2008 which then lead to the Grand Slamhas to be the highlight.
"Wales will be there again this August and they will be right in the middle of a gruelling pre-season right now.
"I'd like to wish them all the best at this summer and at the World Cup, I've been to two of them and experienced all the highs and the lows of international rugby on both occasions.
"It's time for me to look at the next chapter of my life now and I'll be watching at home from my armchair like everyone else for this one, but I'll know the boys will do us all proud."