Purpose: Although hematopoietic stem cell transplantation (HSCT) is a curative treatment for hematologic malignancies, HSCT survivors often experience declined physical function and quality of life (QoL). However, the physical function and QoL changes in acute posttransplant patients remain unclear. This study aimed to monitor changes in physical function and QoL after HSCT. Method: This retrospective controlled cohort study included 107 HSCT patients. Physical function was evaluated weekly from admission to discharge using the de Morton Mobility Index (DEMMI). Impaired physical function was defined as a baseline raw ordinal DEMMI score of < 17 and a decrease of ≥ 2 points. We collected the Visual Analogue Scale (VAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Zung Self-rating Depression Scale (SDS) at enrollment and discharge.Results: Based on the DEMMI scores, 41 patients (38.3%) showed impaired physical function. A notable decrease in the DEMMI score was found in the first week after HSCT. In the EORTC QLQ-C30, physical function differed between the groups at admission and discharge. The good physical function group showed better cognitive function and social function. For the SDS, the impaired physical function group showed significantly higher depression at discharge. Conclusion: A third of the patients showed physical impairment during the acute transplant period. Patients with low physical function suffered more from depression and lower QoL. Evaluating patients’ pretransplant physical function and early detection is needed as impaired physical function mainly occurs at 1 week post-transplant.