Objective:To investigate the long-term clinical effect of deep brain stimulation (DBS) on patients with Parkinson's disease (PD) at Hoehn-Yahr stage 2.5-5 and the differences of clinical effect among patients at different Hoehn-Yahr stages.Methods:A total of 69 PD patients (7 at Hoehn-Yahr stage 2.5, 27 at stage 3, 31 at stage 4, and 4 at stage 5) accepted DBS in Department of Functional Neurosurgery, Affiliated Brain Hospital of Nanjing Medical University from May 2014 to December 2016 were selected for long-term follow-up observation at 60 months after DBS. Unified Parkinson's Disease Rating Scale (UPDRS) was evaluated in the "off" phase of the patients before DBS and the "off" phases of the drugs under DBS start-up and continuous treatment at 6, 12, 24, 36, 48 and 60 months after DBS, respectively; Parkinson's Quality of Life Questionnaire (PDQ-39) and levodopa equivalent dose (LED) data were collected before and 6, 12, 24, 36, 48 and 60 months after DBS. DBS parameters of the patients were collected at 12 months after DBS; the total stimulation power, single pulse average energy and large single pulse energy were calculated. The differences in UPDRS-III scores, PDQ-39 scores and LEDD in these patients before DBS and at different time points after DBS were compared; the differences in UPDRS-III and PDQ-39 scores at different time points after DBS and postoperative DBS parameters at 12 months after DBS in patients at different Hoehn-Yahr stages were compared.Results:Compared with those before DBS, the UPDRS-III scores, PDQ-39 scores and LED were significantly reduced at 6, 12, 24, 36, 48 and 60 months after DBS ( P<0.05). Significant differences in UPDRS-III scores were noted between patients at Hoehn-Yahr stage 5 and Hoehn-Yahr stage 2.5 and stage 3 at 12 and 24 months after DBS ( P<0.05); however, no significant differences in UPDRS-III scores were noted between patients at Hoehn-Yahr stage 5 and Hoehn-Yahr stage 4 at same time points ( P>0.05); and no significant differences in UPDRS-III scores were noted between patients at Hoehn-Yahr stage 5 and patients at Hoehn-Yahr stage 2.5, stage 3, and stage 4 at other time points ( P>0.05). No significant differences in PDQ-39 scores were noted between patients at different Hoehn-Yahr stages at 6, 12, 24, 36, 48, and 60 months after DBS ( P>0.05). No significant difference in total stimulation power, single pulse average energy or large single pulse energy was noted among patients at different Hoehn-Yahr stages at 12 months after DBS ( P>0.05). Conclusion:DBS is long-term effective in improving motor function and quality of life in PD patients at Hoehn-Yahr stage 2.5-5, and patients at Hoehn-Yahr stage 5 do not need higher DBS parameters to obtain similar clinical improved effects as patients at Hoehn-Yahr stage 2.5-4.