We went to Stolac and the Hutovo Blato National Park, then on the scenic coastal route along the Dalmatian coast. A fabulous side trip is along the Peljesac Peninsula where you can visit the tiny famous Dignac wine growing region.
I think the best way is to the coast via Metkovic and then drive up the coastal highway to Split. Last summer we took an inland route to the Croatian city of Vrgorac and up and over the mountains but I think the easiest way is straight to the coast and up the coast. I also don't know the status of the following site. From what I understand this was between Vrgorac and Makarska but don't know for sure and don't know if it has been removed.
I've done this several times, the easiest way is as Barry says above.
Once at the coast you can drive straight up to coast on the Adriatic Highway to Makarska and on to Split, or at Makarska you can get on the new super-fast motorway. If you have more time you can drive via the Peljesac peninsula and get the ferry across from Trpanj to Ploce.
There are also inland routes, but bear in mind that there is a reason why these routes are not used as main routes! Some of those little white roads you see on the map are truly terrifying!
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