In 2011, 2 hikers were killed by grizzly bears (Ursus arctos) in separate incidents on backcountry trails in Hayden Valley, Yellowstone National Park, USA (YNP). Hayden Valley provides prime habitat for grizzly bears and is known to have high densities of bears. During 1970–2017, 23% (10 of 44) of all backcountry grizzly bear–inflicted human injuries and fatalities in YNP occurred in the valley even though it comprises only 1% of the park. In addition, 3 of the last 5 fatal bear attacks in the park occurred in the valley. We evaluated retrospectively whether restrictions and closures on visitor recreational activity would have prevented many of these injuries. We considered prohibitions on recreational activity during seasons when bears forage for specific high-quality foods; potential closures that coincided with the times of day and year bears were most active in the valley; and visitor use restrictions that would have prevented the most common human behaviors associated with grizzly bear–caused human injuries. The food-based closure that may have prevented the most human injuries occurred during middle to late summer when bears scavenge bison (Bison bison) carcasses that result from annual rutting behavior of bison in the valley. However, safety precautions such as hiking in groups of ≥3, remaining on maintained trails, and carrying bear spray would likely reduce the frequency of bear-inflicted human injuries more than most food-based seasonal closures. Our analyses provide broadly applicable findings regarding use of visitor behavior restrictions and seasonal closures to reduce the risk of bear-inflicted human injuries.