Jamie Murray and partner Liezel Huber were beaten 7-6 (8/6) 6-4 by Leander Paes and Cara Black in the mixed doubles final at the US Open.
Scot Murray and American Huber held two set points in the first set tie-break at Flushing Meadows but failed to take their opportunities and fell behind.
Paes and Black, the fifth seeds, then secured a crucial break off Murray's serve before going on their way to victory in one hour and 20 minutes.
It was Murray and Huber's fifth grand slam together having reached last year's US Open semi-finals - when they were beaten by Paes and Meghann Shaughnessy - and the last four of this year's Wimbledon.
Huber - facing her women's doubles partner Black ahead of their semi-final as top seeds against Spain's Anabel Medina Garrigues and Virginia Ruano Pascual - needed to save two break points at 4-3 down in the first set to hold the favourites at bay.
The opening set progressed on serve to a tie-break with Huber and Murray, who won the Wimbledon mixed doubles in 2007 with Jelena Jankovic, earning set points before Paes rallied his team to take a 1-0 lead.
The second set was more clear-cut with Huber and Murray broken to go 3-2 down, leading Paes to serve for the match at 5-4.
'We played great the whole week,' Murray said.
'Last year we came here and it was our first tournament together and unfortunately we lost to (Paes) again in the semi-finals. We were so close.
'I guess I was looking for a bit of revenge today but it didn't happen. But it was a great week.'
Paes has a chance to record a US Open title double when he and Lukas Dlouhy of the Czech Republic face America's Bob and Mike Bryan in the men's doubles final on Friday.
