We stayed at 21c for a weekend wedding. Having been to Louisville several times before and not being impressed with really first class accommodations in Louisville (in spite of Tripadvisor reviews) we were really pleasantly surprised. From the moment that we valet parked our car (each valet was personable and fun) to check-in (front desk staff was friendly and knowledgeable) to our spacious and perfectly kept room we were impressed. And of course the art!! It seemed that every place that we turned there were whimsical pieces that made us smile. The art gallery downstairs is a perfect size. We didn't get bored or get sore feet. And location wise it's really easy to get to and only a block from the Ohio River. Lastly, the hotel restaurant is excellent --- but that's for another review.
We would definitely recommend 21c to anyone coming to Louisville. It's the best in town.