Background and Objectives: EUS-guided ethanol ablation has emerged as an alternative method for pancreatic lesions. Recently, paclitaxel was added to ethanol to assess ablative effects in pancreatic lesions. We performed a systematic review and meta-analysis on EUS-guided ethanol ablation (EUS E) versus EUS-guided ethanol with paclitaxel (EUS EP) ablation for the management of pancreatic lesions. Methods: Comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Google Scholar, and Web of Science databases (from inception to May 2020). The primary outcome evaluated complete ablation of the lesions radiologically and the secondary outcome evaluated adverse events (AEs). Results: Fifteen studies on 524 patients were included in our analysis. The pooled complete ablation rate was 58.89% (95% confidence interval (CI) = 38.72–77.80, I 2 = 91.76%) and 55.99% (95% CI = 44.66–67.05, I 2 = 0) in the EUS E and EUS EP groups ( P = 0.796), respectively. The pooled AE rates were 13.92% (95% CI = 4.71–26.01, I 2 = 83.43%) and 31.62% (95% CI = 3.36–68.95, I 2 = 87.9%) in the EUS E and EUS EP groups ( P = 0.299), respectively. The most common AE was abdominal pain at 7.27% (95% CI = 1.97–14.6, I 2 = 68.2%) and 12.44% (95% CI = 0.00–39.24, I 2 = 81.1%) in the EUS E and EUS EP groups ( P = 0.583), respectively. Correlation coefficient (r) was ‒0.719 ( P = 0.008) between complete ablation and lesion size. Conclusion: Complete ablation rates were comparable among both groups. AE rates were higher in the EUS EP group. Further randomized controlled trials are needed to validate our findings.