Trauma of hospitalization refers to the depersonalizing and stressful experience of a hospital admission and is hypothesized to increase the risk of readmission after discharge. To characterize the trauma of hospitalization by measuring patient-reported disturbances in sleep, mobility, nutrition, and mood among medical inpatients, and to examine the association between these disturbances and the risk of unplanned return to hospital after discharge. This prospective cohort study enrolled participants between September 1, 2016, and September 1, 2017, at 2 academic hospitals in Toronto, Canada. Participants were adults admitted to the internal medicine ward for more than 48 hours. Participants were interviewed before discharge using a standardized questionnaire to assess sleep, mobility, nutrition, and mood. Responses for each domain were dichotomized as disturbance or no disturbance. Disturbance in 3 or 4 domains (the upper tertile) was considered high trauma of hospitalization, and disturbance in 0 to 2 domains (the lower 2 tertiles) was considered low trauma. The primary outcome was readmission or emergency department visit within 30 days of discharge. The association between trauma of hospitalization and the primary outcome was examined using logistic regression, adjusted for age; sex; length of stay; Charlson Comorbidity Index Score; Laboratory-Based Acute Physiology Score; and baseline disturbances in sleep, mobility, nutrition, and mood. A total of 207 patients participated, of whom 82 (39.6%) were women and 125 (60.4%) were men, with a mean (SD) age of 60.3 (16.8) years. Among the 207 participants, 75 (36.2%) reported sleep disturbance, 162 (78.3%) reported mobility disturbance, 114 (55.1%) reported nutrition disturbance, and 48 (23.2%) reported mood disturbance. Nearly all participants (192 [92.8%]) described a disturbance in at least 1 domain, and 61 participants (29.5%) had high trauma exposure. A statistically significant 15.8% greater absolute risk of readmission or emergency department visit was found in participants with high trauma (37.7%; 95% CI, 25.9%-51.1%) compared with those with low trauma (21.9%; 95% CI, 15.7%-29.7%), which remained statistically significant after adjusting for baseline characteristics (adjusted odds ratio, 2.52; 95% CI, 1.24-5.17; P = .01) and propensity score matching (odds ratio, 2.47; 95% CI, 1.11-5.73; P = .03). Disturbances in sleep, mobility, nutrition, and mood were common in medical inpatients; such trauma of hospitalization may be associated with a greater risk of 30-day readmission or emergency department visit after hospital discharge.