All four West Coast Main Line tracks between London Euston and Watford Junction will close from midnight on 19 September until 4pm on 20 September while a deteriorated footbridge is removed.
Network Rail announced the planned closure on 4 September. The adjacent London Overground Lioness line beneath Oxhey Grange footbridge will also close during the removal work.
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Network Rail said Oxhey Grange footbridge was closed on 26 July after inspections found it had deteriorated faster than expected.
The closure is scheduled to run from just after midnight on Saturday 19 September until 4pm on Sunday 20 September.
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