It depends on the time of year and water flows for me, usually I will fish upstream to start the day and then downstream on the way back to the car. Ideally, if I can find a way to cross the river (or can wade accross) I like to fish the opposite bank coming back down to the car. though there may be some areas of big rivers where you gotta go a long way to get accross and you don;t want to be stuck on the wrong side and not be able to get back to your car without having to take a long hike. Not that I have ever done anything like that
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