La Crosse Regional Airport has limited scheduled service, mainly connecting to Chicago O'Hare and Minneapolis. Most visitors driving from the Twin Cities (about 2.5 hours north on US-14/61) or from Milwaukee (about 3 hours east on I-90) find the drive more practical than flying. From Madison it's around 2.5 hours.
Amtrak's Empire Builder — the Chicago to Seattle and Portland train — stops at La Crosse twice daily in each direction. The station is at the north end of downtown, walkable from most hotels. For travelers on the long-distance Chicago-Seattle route, La Crosse makes a natural overnight stop to break the journey.