transportation from Prague- Little Quarter to get to airport?

Metro is not running at that time. Trams are on night departures running about every hour or so. From Dejvicka you would have to catch bus 119 to the airport. I am not sure if it is running at night and if so then also about every hour. My recommendation: taxi. AAA would be the one I would recommend. Drivers speak English and are honest which is not very usual among taxi drivers in Prague.

This is the Prague transportation website: http://www.dpp.cz/en/ You should be able to get the night schedules here, both for the trams and for the 119 bus..
Also, Prague's airport is small, well organized and should not be very busy at that hour. You can probably get away with getting there as little as one hour early, especially if on one of the budget airlines whose desks probably won't be open until then.

Let me amend my prior post. I just checked the schedule myself, and the first AM bus from Dejvicka leaves at 4:58Am, takes about 20 minutes to the airport. You will have to ask yourself if you are comfortable with only 40 minutes to board. Depends on airline.
Also, it is walkable from the Little Quarter to the bus stop, depending on where you are starting from and how much you are carrying. For example, about 1.75 miles from the Lennon Wall.

Prague airport is not huge but neither it is small. It has two terminals. Generally flights to another Schengen country fly from terminal 2, all others from terminal 1. Bus 119 stops first at terminal 2, then at terminal 1. It would be very unpleasant to walk with luggage if you miss your terminal.

I just read that I might be able to call a Shuttle Co? If that's not available I think I will go with the AAA taxi suggestion or hotel transport. I don't want to be walking around late at night with my luggage not knowing where I'm going. And certainly do not want to miss my flight home. Any other suggestions are always apprecieated. Thanks again. Jacque

Hi Jacque. I fly out of PRG 1-3 times a year back to the USA. And sometimes I have taken early flights like yours. You don't need to be at the airport 3 hrs in advance. The check in counters don't even start processing until 2hrs before each flight. And you can't check in online for most flights to USA. There are check-in kiosk computers for some airlines near the check-in counters. I've used them to print out boarding passes but you still need a person at the counter to check your luggage which again isn't any earlier than 2 hrs before the flight.