The pile-up that closed the A34 dual carriageway outside Oxford for more than 17 hours could have cost the area £5m to £10m.
That is the estimate from Keith Slater, Oxford's Chamber of Commerce president, who fears the cost to the local economy could have been massive in the run-up to Christmas.
The crash early on Tuesday closed the road and prevented thousands of people from reaching Oxford, reducing custom in city centre shops.
Shops were quiet and there were large numbers of parking spaces available.
Two lorries and a car transporter were involved in the smash and the driver of the transporter was yesterday in a critical but stable condition at the John Radcliffe Hospital.
Mr Slater said: "If you look at all the aspects of the crash, the people involved, the vehicles involved, the emergency services' time, the loss of sales, we could be talking about £5m to £10m as the result of that one accident.
"The centre of Oxford was quite quiet for this time of year, especially from mid-morning. Takings in many stores were down something like 10 per cent."
Mr Slater said the Chamber of Commerce had been calling for the A34 to be upgraded for some time.
He added: "For most people who use it, it's obvious something needs to be done. It wasn't designed for the amount of traffic it takes -- many of the bends are unsuitable for 70mph dual carriageway traffic."
Bill McCardle, chief executive of city centre management company OX1, said traders were still assessing the impact of the crash. The accident, which happened at about 4.30am, involved a 44-tonne articulated lorry which went out of control and ended on its side, blocking the southbound carriageway between the Peartree and Botley interchanges.
A transporter carrying Jaguar cars struck it, shedding its load, and a third vehicle, a 20-tonne lorry, crashed into the wreckage, also ending on its side.
The southbound carriageway was closed for almost the rest of the day, and huge queues built up as drivers struggled to find alternative routes.
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