Make sure this kind of trip is suitable for you. If you don't like driving (or being a passenger in a road vehicle), this simply isn't the trip for you. RV vacations typically involve plenty of time on the road; also, maneuvering these large and often unwieldy contraptions isn't for everyone. And if small, enclosed places make you claustrophobic, this might not be your preferred getaway.
Plan your trip out in detail and make all the proper advance reservations at parks, campgrounds and any other locales. It can be misleading to think that taking to the road in an RV somehow gives you unlimited flexibility. Most campgrounds and parks have limited space/hookups available for RVs, and you don't want to be trolling around in the dark after a long day's drive searching desperately for an appropriate place to hunker down.
Choose the ideal traveling companion(s), especially if you're sharing one RV! Any stress or tension will be magnified in an RV, so make sure you're traveling with people you get along with seamlessly; this is probably not the time to try your first trip with a person or persons.
If you're traveling with children, make certain to lay down some very clear and concrete ground rules before the trip, for everyone's safety. Teaching children to remain buckled up and reasonably quiet during drives is a good start; you won't want any unnecessary distractions while trying to maneuver an RV.
Don't overdo the daily driving. RVs get poor gas mileage and are also slower than most other vehicles, so arranging a schedule where you have to drive 500 miles a day is probably not wise planning.
Try to arrange a spectacular final destination for your journey. While it may be the "journey and not the destination" that is crucial to RV getaways, any trip will be more exciting if you know someplace like the Grand Canyon, Florida Keys or Yellowstone National Park is waiting at the finish line.
Bring some items along for both outdoor and indoor fun. After being inside, it can be nice to get out and explore with a metal detector, fly a colorful kite or do some birdwatching with binoculars; conversely, you'll want to be prepared for unfriendly weather by bringing playing cards, a radio, board games, books and any other indoor activities you enjoy.
