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Background: Roux-en-Y gastric bypass (RYGB) is considered effective for weight loss and for treatment of many obesity-related metabolic diseases. Ghrelin is an essential orexigenic peptide that plays an indispensable role in controlling body weight and energy homeostasis of post-operative patients. This systematic review and meta-analysis aimed to investigate changes in the level of fasting total ghrelin following RYGB., Methods: A systematic literature search of PubMed, EMBASE, and the Cochrane Library until April 2018 with keywords "ghrelin" and "gastric bypass" was performed in accordance with the MOOSE guidelines and PRISMA statement. Three reviewers independently selected the studies and extracted data. Quality assessment of the included studies was undergone. A random effects model was employed to calculate overall effect sizes. Subgroup analyses and meta-regression were subsequently performed., Results: Sixteen studies with 325 patients were included. We found ghrelin levels had an increasing tendency (SMD = 0.30; 95% CI = 0.04 to 0.57) despite moderate heterogeneity (I 2  = 58%). Subsequent subgroup analysis indicated that ghrelin levels decreased (SMD = - 0.49; 95% CI = - 0.98 to 0.00) in the short term (≤ 3 months) and increased (SMD = 0.46; 95% CI = 0.22 to 0.69) in the long term (> 3 months) after RYGB. Meta-regression showed that gastric pouch volume, alimentary limb length and biliopancreatic limb length were not associated with changes in ghrelin levels., Conclusion: Fasting total ghrelin levels decreased in the short term (≤ 3 months) and increased in the long term (> 3 months) after RYGB.