Nearly half of Welsh trade is with the European Union and the nation will be "better off" if the UK remains in, David Cameron has said.
Treasury officials have estimated that around 100,000 jobs in Wales could be linked to exports to EU countries.
The Prime Minister is visiting Cardiff in the latest campaign stop to persuade voters that Britain should remain part of the 28-member bloc.
"My view is clear: we are better off, safer and stronger in the EU. Wales will be better off because businesses will continue to have full access to the free trade single market," he said ahead of the visit.
"It is this market of 500 million consumers that brings jobs, investment and lower prices. The single market brings jobs because it's our trade with Europe that helps Welsh businesses to grow and take people on, especially in key industries like energy, aerospace, pharmaceuticals, and high-tech manufacturing.
"Leaving, on the other hand, is a leap into the dark. Those who want to leave can't tell you what the aftermath of an exit from the EU would look like.
"They can't say how much of the £500 billion of trade the UK enjoys with EU countries would be put at risk. If we vote to stay in, we know exactly what we'd be getting - not just full access to that single market, but the best of both worlds in terms of our relationship with the EU."
Mr Cameron will point to investment in Wales from firms like Aldi and Airbus and claim remaining in the EU would boost the local economy.
Around £5.8bn worth of goods were exported from Wales to the EU in 2014, which accounted for 43% of its overseas trade.
Welsh Secretary Stephen Crabb said: "The Welsh economy is stronger because we are in the EU. World leading companies choose Wales because of the excellence of our manufacturing base and the link we provide into the single market.
"The historic deal secured by the Prime Minister last week enables Wales to have the best of both worlds - being part of a powerful trading bloc of 500 million people while ensuring that we have a special status which means we are not part of an ever closer political union."