The A419's southbound carriageway through Swindon has been closed.
The busy route into town is currently shut from the Lady Lane junction to the A420 junction at White Hart so that much-needed construction work can be carried out.
Work started at 8pm on Friday and will last until 6am on Monday. This follows the northbound carriageway being closed from the evening of September 1 until September 4 for the same reason.
Diversions are in place, and traffic will leave the A419 at the Lady Lane junction and re-join at the A420 White Hart roundabout.
Part of Highworth Road heading into Swindon between the Honda and Rat Trap roundabouts is also closed, with two-way traffic lights managing the flow of vehicles.
The work, which involves replacing bridge parapets and structural repairs, had been arranged to avoid clashes with Swindon Town FC home matches.
Andrew Gale, National Highways' service manager, said: "We appreciate roadworks can be frustrating, but we've been working with both Swindon Borough Council and Swindon Town Football Club to ensure as little disruption as possible.
"We've been communicating with local businesses and communities, we're keeping the closures to an absolute minimum and we thank all drivers in advance for their co-operation and patience while we carry out these essential works."