Specimens can be kept in 10-gallon terraria or plastic tubs on a substrate of 2 to 4 inches of shredded aspen or loose sand. The substrate should never be allowed to become wet, but a small bowl of water should be kept in the terrarium. Maintain a temperature of 75 to 85 degrees Fahrenheit, with a slight drop at night. Neither a basking light nor undertank heating is necessary. Specimens will spend most of the day burrowed under a piece of bark or other decoration and come out mostly at night. Two or three specimens can be kept together.

Unlike eastern hognoses (Heterodon platirhinos) that prefer toads, the western hognose feeds readily on small rodents, making it much easier to maintain as a terrarium species. Captive-bred specimens generally take small mice soon after hatching, while large adults will take hoppers and adult mice. Wild-caught specimens often carry a heavy parasite load and require worming. They also may prefer lizards to mice (anoles generally are accepted). If your specimen proves to be a lizard-eater, it can be switched from lizards to mice by rubbing lizard scent (such as droppings) on mice offered as food. Most specimens eventually switch to rodents.

Like other hognoses, this species has a pair of enlarged teeth in the upper jaw, but they technically are not venomous. Some keepers have shown minor allergic reactions when bitten.