The men – one in his 20s and one in his 30s, it is believed – suffered cardiac arrests after taking part in the annual race, organisers said.
Medical emergency teams at the finish line attended to the pair before the men were taken to the University Hospital Wales in Cardiff, where they later died.
About 25,000 runners took part in the half marathon.
Organisers Run 4 Wales said the deaths were the first fatalities in the 15-year history of the race, which is the second-biggest half marathon in the UK behind Newcastle’s Great North Run.
Chief executive Matt Newman said: “This is a terrible tragedy for the families. Our deepest sympathies go out to their family and friends.
“The emergency services reacted to this terrible situation with great speed and professionalism. Everyone connected with the race is devastated.”
Thousands of spectators lined the 13.1-mile route, which took in the Wales Millennium Centre, the Cardiff Bay Barrage and Roath Park.
Agencies contributed to this report
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