ObjectivesFew studies have evaluated the mechanism of serious injury in acute hospitalization. Thus, the association between fall-related serious injury and activity during falls in acute care hospital remains unclear. Herein, we investigated the relationship between serious injury caused by fall and activity at the time of the fall in an acute care hospital.MethodsThis retrospective cohort study was conducted at Asa Citizens Hospital. All inpatients aged 65 years and older were eligible for the study, which was conducted from April 1, 2021, through March 31, 2022. The magnitude of the association between injury severity and activity during the fall was quantified using odds ratio.ResultsAmong the 318 patients with reported falls, 268 (84.3%) had no related injury, 40 (12.6%) experienced minor injury, 3 (0.9%) experienced moderate injury, 7 (2.2%) experienced major injury. Moderate or major injuries caused by a fall was associated with the activity during the fall (odds ratio: 5.20; confidence intervals: 1.43–18.9, p = 0.013).ConclusionThis study recognizes that falling during ambulation caused moderate or major injuries in an acute care hospital. Our study suggests that falls while ambulating in an acute care hospital were associated not only with fractures, but also with lacerations requiring sutures and brain injuries. Among the patients with moderate or major injuries, more falls occurred outside the patient’s bedroom as compared with patients with minor or no injuries. Therefore, it is important to prevent moderate or major injuries related to falls that occur while the patient is walking outside their bedroom in an acute care hospital.