Objective To investigate factors associated with achieving minimal clinically important difference (MCID) in upper limb motor function after rehabilitation in patients with acquired brain injury (ABI). Methods Patients receiving rehabilitation therapy in the Third Affiliated Hospital of Sun Yat-sen University Hospital between April 2015 and October 2022 were retrospective selected. Upper limb motor function was assessed using the Fugl-Meyer Assessment- Upper Extremity (FMA-UE) at baseline and discharge. An increase of ≥5 points in the FMA-UE score was defined as achieving MCID. Logistic regression analyses were used to identify factors associated with achieving the MCID. Stratified analyses were conducted based on baseline FMA-UE scores (≤21 vs. >21). Results A total of 236 patients were included. Among them, there were 156 males and 80 females; 138 cases met the MCID, and 98 cases did not; 115 cases had FMA-UE scores ≤21, and 121 cases had FMA-UE scores >21. FMA-UE scores significantly improved after rehabilitation therapy compared with admission scores [21 (12, 36) vs. 29 (18, 47) scores, P<0.001]. The results of the multi-factor logistic analysis showed that in the severe impairment group, length of stay was associated with achieving MCID [odds ratio=1.028, 95% confidence interval (1.004, 1.052), P=0.019]. In the mild-to-moderate impairment group, female sex was negatively associated with achieving MCID [odds ratio=0.306, 95% confidence interval (0.107, 0.872), P=0.027]. Conclusions Different lengths of stay and genders may affect the achievement of MCID in ABI patients. Further prospective studies are needed to validate these findings.