INTRODUCTION: EUS-guided needle-based confocal laser endomicroscopy (nCLE) provides real-time histology assessments and has been reported as an adjunctive tool that can be performed in the same session as EUS-fine needle aspiration. We aimed to perform a systematic review and meta-analysis regarding the diagnostic performance, success rate, and complications of nCLE in pancreas cysts. METHODS: This is a systematic review and meta-analysis following the PRISMA-P principles. Literature was systematically searched in February 2019 by two independent investigators in 3 major databases including PubMed, Embase, and Web of Science by using the terms “confocal endomicroscopy” AND “needle” AND “pancreas cyst.” The search was limited to English-written and in vivo human studies. Additionally, investigators manually reviewed the references of the primary identified studies for other eligible articles. The meta-analysis of success rate, complication rate, pooled diagnostic parameters with the respective 95% confidence interval (CI) of nCLE for diagnosis of pancreas cysts were performed. RESULTS: Of the 159 initially screened studies, 11 studies had 288 patients with pancreatic cystic lesions enrolled. The estimated overall success rate and adverse event rate with random effects model were 96% (95% CI: 92–95%) and 11% (95% CI: 7.5–16%), respectively. There were 7 studies which included 176 patients that reported the diagnostic parameters of nCLE for diagnosis of mucinous pancreas cyst. The estimated diagnostic odd ratio (DOR) was 50 (95% CI: 18.92–132.16). The estimated area under curve (AUC) was 0.939 (95% CI: 0.89–0.992) and AUC for SROC was 0.84 (95% CI: 0.72–0.98). The estimate sensitivity and specificity were 0.77 (95% CI: 0.62–0.87) and 0.91 (95% CI: 0.81–0.96), respectively. The meta-analysis estimated the prevalence rate of mucinous cysts to be 57% (95% CI: 43%–71%). The positive predictive value (PPV) and negative predictive value (NPV) were 0.91 (range: 0.86–0.95) and 0.72 (range: 0.62, 0.84), respectively. I2 index showed no heterogeneity between studies in success rate, adverse event rate, DOR, and specificity. However, heterogeneity was detected in sensitivity, PPV, and NPV between studies. CONCLUSION: nCLE has high sensitivity, specificity, PPV, and NPV for differentiating mucinous pancreas cyst from the other cystic lesion. However there is an increased adverse rate compared to standard EUS-FNA. Measures and methods to decrease the adverse event rate should be further investigated.