Objective To investigate the efficacy of Madopar on vascular parkinsonism with paroxysmal atrial fibrillation(VPD+ PAF)in elderly patients and its effect on the autonomic nervous system. Methods We recruited 50 patients aged over 60 with VPD + PAF into this randomized controlled trial.Based on sinus rhythm recorded by 24 hour ambulatory electrocardiogram ,individuals with an average heart rate below 60 times per minute were assigned into a sinus bradycardia group (n＝15)and those with a normal average heart rate were randomly assigned into a normal rate group (n＝20)or a control group (n＝ 15)by drawing lots.The control group was given routine care for 12 weeks ,while the other two groups were treated with Madopar plus routine care for 12 weeks. The three groups were examined using UPDRS-3 ,dynamic electrocardiogram ,heart rate variability , echocardiography ,and plasma acetylcholine(ACH)levels 1 day before treatment ,4 weeks and 12 weeks after treatment ,and atrial fibrillation frequency 2 weeks after treatment. Results UPDRS-3 scores decreased significantly in the sinus bradycardia group and the normal rate group after treatment for 4 weeks and 12 weeks ,compared with those before treatment (P＜0.05) ;UPDRS-3 scores in the control group did not show statistically significant changes at week 4 after treatment but decreased significantly at week 12(P＜0.05).UPDRS-3 scores in the sinus bradycardia group and the normal rate group were lower than those in the control group after treatment for 4 weeks and 12 weeks(P＜0.05). The total effectiveness rates in the sinus bradycardia group (86.7%,n＝13)and the normal rate group(85.0%,n＝17)were higher than the rate in the control group(53.3%,n＝8)(P＜0.05).Ach levels in the sinus bradycardia group and the normal rate group significantly decreased after treatment for 4 weeks and 12 weeks ,compared with before-treatment levels ,but no significant difference was observed between before-and after-treatment levels in the control group. Frequencies of AF in the sinus bradycardia group(5.6 ± 3.5)and the normal rate group(5.2 ± 4.1)were significantly lower than in the control group(8.4 ± 5.2)(P＜0.05). Conclusions Madopar can depress vagus nerve activity ,relieve VPD+ PAF symptoms ,and reduce the frequency of AF ;Heart rate variability and ACH level are potential predictors of clinical efficacy of Madopar in VPD patients.