Abstract: Objective To investigate the efficacy of short-term full-dose prophylaxis in adult Chinese patients with severe hemophilia A. Methods Thirteen adult Chinese patients with severe hemophilia A receiving on-demand or low-dose prophylaxis underwent ultrasound examination of the target joints and evaluation of Hemophilia Joint Health Score (HJHS). The data of annual bleeding episodes in the period of on-demand or low-dose prophylaxis were collected retrospectively from the patients, and the changes in bleeding and joint condition (ultrasound findings of the target joints and HJHS) were observed during short-term full-dose prophylaxis. The activity intensity of the patients was assessed using the IPAQ questionnaire, and the 72 h FVIII trough activity was measured during full-dose prophylaxis. Results The median age of the 13 patients was 26.0 (20.5-29.0) years. For full-dose prophylaxis, the patients received a median therapeutic dose of 31.0 (29.1-33.0) IU/kg, administered for 3 times per week; the median 72 h FVIII trough activity of patients was 1.7% (1.3-3.4%). During the follow-up period for 3 months, the annual bleeding rates (ABR) and annual joint bleeding rates (AJBR) decreased significantly in all the patients (P=0.001 and 0.001, respectively), but zero bleeding was achieved in only 4 patients (30.8%) and zero joint bleeding in 7 patients (53.8%); 9 patients (69.2%) still experienced breakthrough bleeding. The damage severity of target joints assessed by ultrasound and HJHS in 6 patients (46.2%)was worse than before and no obvious progression of target joints damage was found in 7 patients (53.8%). Compared with the patients without progression, the patients with worsened joint damage had poorer baseline joint condition, higher bleeding frequencies before and during the follow-up, a higher intensity of physical activity, and a lower baseline FVIII activity. Conclusion At present, although short-term full-dose prophylaxis can significantly reduce the bleeding and partially prevent the progression of joint damage, it is not yet possible to achieve the goal of zero bleeding for all adult patients with severe hemophilia A in China, nor can it completely prevent further joint damage. For adult patients with different clinical bleeding phenotypes, joint conditions and physical activity intensity, individualized therapy involving additional evaluation methods should be implemented, and physiotherapy and surgical intervention can be considered when necessary.