There is currently limited evidence supporting the use of needle-based confocal laser endomicroscopy in pancreatic cystic lesions. Aim of this study was to provide a pooled estimate of the diagnostic performance and safety profile of this technique in patients with pancreatic cysts. Computerized bibliographic search on the main databases was performed through November 2019. Pooled effects were calculated using a random-effects model by means of DerSimonian and Laird test. Primary endpoint was diagnostic accuracy. Secondary outcomes were pooled sensitivity, specificity, and mean procedural time. Ten studies enrolling 536 patients were included. Eight articles, of which five prospective series, compared confocal laser endomicroscopy to cytology/cystic fluid analysis. Most patients were female and body/tail was the most frequent location of pancreatic cysts. Mucinous cysts were prevalent in most of the included studies. Diagnostic accuracy with confocal laser endomicroscopy was 88.6% (83.7-93.4%) and sensitivity analysis according to study quality, design, and treatment arms confirmed the above reported result. Pooled sensitivity and specificity were 82.4% (74.7-90.1%) and 96.6% (94.3-99%), respectively. Both accuracy and sensitivity resulted higher in patients with mucinous cysts (91.4 and 94.9%, respectively). Confocal laser endomicroscopy clearly outperformed fine-needle aspiration in terms of diagnostic accuracy (odds ratio 3.94, 1.58-9.82; P = 0.003). A mean of 6.094 minutes (4.91-7.26) was needed to complete the procedure and no significant adverse event was registered. Our meta-analysis speaks in favor of the use of needle-based confocal laser endomicroscopy as a safe and effective tool in the diagnostic algorithm of pancreatic cysts.