Strike action is set to disrupt train services through Lockerbie on Hogmanay.
And it marks the start of a series of walkouts by train managers which could last several months.
Train managers in the Rail, Maritime and Transport (RMT) Union at Avanti West Coast had called off walk outs over the festive period after Avanti West Coast made a new offer.
However, members overwhelmingly rejected the deal, which the train operator had hoped would resolve a dispute over rest day working.
Train managers will now strike on New Year’s Eve, January 2 and Sundays between January 12 and May 25.
An RMT spokesperson said: “Our members have resoundingly rejected Avanti’s latest offers in two referendums and sustained strike action is now the only way to focus management’s minds on reaching a negotiated settlement with the union.”
Avanti runs services through Lockerbie and had warned the festive strikes would lead to the timetable being “reduced significantly” and what train services did run would be busy.
A spokesperson said: “This strike action will cause significant disruption to our customers making journeys on the West Coast Main Line over an extended period.
“We’re disappointed our train managers who are RMT members have voted to decline the very reasonable, revised offer made to them to resolve the rest day working dispute and avoid inconveniencing our customers.
“We remain open to working with the RMT to resolve the dispute.”