The Dragons academy product was identified at an early age as he went on to represent Wales throughout the age grades and captained the U20s in the 2007 Six Nations Tournament.
The 28-year-old began his time with the Region in 2005 and has made an outstanding contribution with over 160 appearances for the Dragons. Before his time with the Men of Gwent, Smith made a number of appearances for premiership side Newport RFC.
Commenting on his retirement, Smith said: "I am utterly disappointed and devastated that I have been forced to retire through injury but I feel that the medical advice given to me cannot be ignored.
"It's been a great honour to play for my home Region. I have supported both Newport RFC and the Dragons since I was young so playing at Rodney Parade was a massive privilege for me.
"I will miss running out in front of our fantastic fans and look forward to standing alongside them cheering on the boys in the future. To leave now when the potential within the group is about ready to come to fruition is hard to take. I have enjoyed my role as a senior member of the squad helping guide the next generation of players into what is certain to be an exciting time for them with both club and country.
"I would like to take this opportunity to thank my wife, family and close friends who have supported me throughout my rugby career and most recently over the past few weeks, which has been a stressful time for me.
"I would also like to thank the medical team at Newport Gwent Dragons - they too have been a fantastic support.
"Looking forward I am not sure what the future holds for me or even what I want to do, but I am planning on taking some time to reflect on my opportunities, wherever that may be.
"To be lucky enough to have played our sport for a living is something I cannot describe, the memories I have gained along the way will last a lifetime as well as the values the game instills.
"I wish the squad and everyone at the region all the very best for the future."
Director of Rugby, Lyn Jones added: "We are all so upset at the news of Ashley's forced retirement.
"Over his ten years at Rodney Parade, he has been a credit to the Region, himself and his family. We will miss his maturity, football, decision making and his experience. It's a big blow for us, but Ashley has made the right decision for himself and his family.
"We wish him well for the future."
Newport Gwent Dragons director Jim McCreedy commented: "Ashley is a true credit to our Region.
"He has been a player here at Rodney Parade for over ten years and it is sad to see such a fantastic person and talented player hang up his boots.
"I am sure that everyone involved at the Region will join me in wishing him all the best with his future endeavours."