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The airport is approximately 43 miles or 70km, about 50 – 60 minutes driving along the A22 motorway, from Portimão. The route is well signposted. Be aware that TOLLS are payable for trips along the A22 road. Toll collection is electronic only, Portuguese registered cars do not have to be fitted with a tag, as there are various options to pay the tolls after you made a journey. This is however somertimes cause problems for some visitors when returning cars to the airport. Your car hire company will advise. Most now provide pre-paid toll transponders.
The parallel N125 road will save you the 8 cents per km toll but take longer.
While driving in Portimão be sure to have a navigation system to aid given that there are many one-way streets specially around the city center.