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Flying to Cape Girardeau:

Yes, it can be done.  There is a regional airport with three flights daily, connecting through St. Louis.  An affiliate of American Airlines runs this service.   Once you arrive at the Cape Girardeau Regional Airport, you can call for a local taxi to take you to your hotel ($10) or rent a car at the Cape airport.

BUT As one who flies a lot to and  from the Cape area, I personally prefer to fly into St. Louis Lambert International Airport (STL) or Memphis (MEM) and rent a car to drive to Cape Girardeau.  Less waiting and I love the drive.  And often it's less expensive.

If you don't want to drive, you can take the Bootheel Area Rapid Transit  (BART) van from the St. Louis airport (only) directly to your hotel in Cape for $65 one way.  Be warned that there are sometimes long waits before the van departs.  Call (573) 335-0844 to make BART reservations.

St. Louis airport is just 2 hours north of Cape (130 miles, mostly interstate, 1/3 built up areas, 2/3 country with rolling hills).  The Memphis International Airport is 3 hours south (175 miles, mostly interstate and mostly rural flatlands).  Use Mapquest to find more detailed directions, but the map below can help with orientation  (http://www.mapquest.com).

A general orientation map, from Mapquest.  Find Cape Girardeau, MO near the center of the map.  It is located between I-55 and the Mississippi River.