Aims:To assess the efficacy and safety of adjuvant treatment with entacapone in the treatment of later Parkinson's disease (PD) patients with motor fluctuation. Methods: We conducted a systematic review of relevant studies from 8 databases to June 23, 2016. Results: Fourteen studies were included in this review (n = 2,804). The results showed that compared with placebo, adjuvant therapy with entacapone significantly increased on time (p < 0.01) and reduced off time (p < 0.01), the required levodopa (LD) dose (p < 0.01) and improved Parkinson's Disease Rating Scale (UPDRS) scores (activities of daily living score: p < 0.01; motor score: p < 0.01; UPDRS I-III score: p > 0.05). However, the withdrawal (OR 1.44, 95% CI 1.10-1.89, p < 0.01) due to adverse events and adverse events rates including nausea (OR 2.23, 95% CI 1.56-3.20, p < 0.01), urine discoloration (OR 14.99,, p < 0.01), gastrointestinal disorder (OR 2.6, 95% CI 1.89-3.57, p < 0.01) and dyskinesia (OR 2.00, 95% CI 1.56-2.58, p < 0.01) increased in patients with entacapone compared with those given a placebo . Conclusions: This metaanalysis suggests that the entacapone used as adjuvant therapy to LD is effective in the management of later PD with fluctuation. However, patients on entacapone had a higher frequency of adverse events than those on placebo but no occurrence of severe adverse reactions.