Objective To investigate the effect of using prophylactic antidepressant treatment with citalopram on motor function recovery in patients with acute cortical infarction. Methods The patients with first-ever acute middle cerebral artery territory cortical infarction and with upper limb motor deficits within 24 h after onset were enrol ed prospectively. They were randomly divided into either a citalopram group or a control group. On the basis of conventional treatment, the citalopram group was given citalopram hydrobromide tablets oral y (20 mg/d) within 48 h after onset of stroke for 30 d. The 17-item Hamilton Depressive Rating Scale (17-item HDRS) was used to conduct the assessment of depressive symptoms before and after treatment. The National Institutes of Health Stroke Scale ( NIHSS ) and Fugl-Meyer Assessment (FMA) hand motor function score were used to conduct function assessment before and after treatment. Results A total of 66 patients were enrol ed in the analysis, including 32 patients in the citalopram group and 34 in the control group. There was no significant difference in baseline clinical data between the 2 groups. The baseline stroke severity of al patients was moderate (NIHSS score 5-15). Compared with baseline level at day 30 after the treatment, the HDRS score of the citalopram group was improved significantly (6. 70 ± 3. 58vs. 9. 86 ± 3. 48; t= 3. 380, P= 0. 001 ). However, there was no significant difference with the control group after treatment (6. 70 ± 3. 58 vs. 8. 12 ± 2. 96;t=1. 745, P=0. 086). The NIHSS scores in the citalopram group and the control group were decreased respectively (4. 30 ± 1. 88 vs. 2. 00 ± 1. 24;t=5. 900, P<0. 001). The hand FMA scores were increased significantly (4. 00 ± 0. 70 vs. 1. 42 ± 1. 91;t=7. 197, P<0. 001). There was significant difference between the 2 groups. In addition, the hand motor function score at day 30 after treatment was more than 25% of the baseline recovery in 14 patients of the citalopram group (43. 8%) and in 5 of the control group (14. 7%). The citalopram group was significantly higher than the control group (χ2 =6. 783, P=0. 009 ). Conclusions Early prescription of citalopram can significantly promote the motor function recovery in acute cortical infarction patients with moderate motor deficit and its mechanism may not be associated the antidepressant effect.