The sixth seeded Indian duo lost 2-6 3-6 in the summit clash of the Euro 3,204,745 clay court event.
Such was the domination of the veteran American pair that Indians could not earn a single break point opportunity.
The Indians lost their serve twice in the opening set and once in the second.
Bhupathi and Bopanna were playing their second final of the season and first together.
Bhupathi had won the Dubai event with Michael Llodra while Bopanna had triumphed at Marseille, France with Colin Fleming.
With their runners-up finish, Bhupathi and Bopanna split 76,060 euros as prize money and earned 600 ranking points each.
Rome Masters: Bhupathi-Bopanna lose doubles final to Bryan Brothers
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