If you are in good shape and can only do one hike in Boulder, hiking the full Mesa Trail is a great option. You will see the arid high desert environment, thick old-growth forest, incredible rock formations that have made Boulder famous, and great views of the city and Eastern plains. It is a little over 7 miles from end to end and can be completed in two to three hours.
Hiking the entire Mesa Trail does require some coordination, as it is an end to end hike. You can either start at the North end, at the Chautauqua Trailhead. Or you can start at the South end, at the South Mesa Trailhead. With whichever option you choose, you will need to leave a vehicle at the other end to shuttle back, or arrange for transportation. If you are feeling especially ambitious, you could certainly hike it both ways for about a 14 mile hike!
From the North
If starting from the North, you will start at the Chautauqua trailhead. You can follow the wide Mesa Trail directly south from the parking lot, or you can take the more scenic (but more strenuous) Bluebell Trail towards the Flatirons and connect with the Mesa Trail in a mile or so. Other than the Bluebell Trail detour, you should always just follow signs for the Mesa Trail. It is around 7 miles to the southern finish.
The majority of the miles in the middle will be in the forest and provide a lot of shade. The first mile and last couple miles are quite exposed so you should prepare to be in the sun.
Here is the elevation profile from North to South:
From the South
If starting from the South, you will begin by crossing a bridge over South Boulder creek followed by a long 2 mile ascent through an arid section with great views of the Flatirons and foothills. After that first couple miles, the trail will be a little gentler, with lots of slight uphill and downhill sections in the forest before the long descent in the last mile as you approach Chautauqua.
Here is the elevation profile from South to North:
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