Introduction: Barrett’s esophagus (BE) is a precursor condition to esophageal adenocarcinoma (EAC), resulting in transformation of the squamous epithelium of distal esophagus to columnar-lined epithelium with intestinal metaplasia (IM). Liquid nitrogen spray cryotherapy (LNSC) is a non-contact method of BE eradication and has been used both as primary and salvage therapy. We conducted a systematic review and meta-analysis to assess the safety and efficacy of LNSC. Methods: We searched multiple databases from inception through December 2021 to identify studies on use of LNSC for Barrett’s neoplasia. Pooled estimates were calculated using random-effects model and results were expressed in terms of pooled proportions with relevant 95% confidence intervals (CIs) of complete eradication (CE) of dysplasia(D), high grade dysplasia (HGD) and IM. We also assessed pooled rates of therapeutic failures as well as post procedure complications including strictures, pain and perforation events. Results: Fourteen studies with 666 patients were included in our final analysis. (Figure) Overall pooled rates of CE-D, CE-HGD and CE-IM were 80.8% (CI 77.4-83.8; I2 62), 87% (CI 82-90.8; I2 60) and 55.8% (CI 51.7-59.8; I2 73) with follow up ranging from 4.25 months to 69.7 months. Among LNSC naïve patients with prior history of endoscopic resection, the rates were 83% (CI 73.6-89.5; I2 46), 76% (CI 65.1-84.3; I2 38) and 71.8% (CI 60.9-80.7; I2 0). In patients with follow up beyond 24 months, the rates were 78.8% (CI 72.4-84.1; I2 84), 85.2% (CI 73.1-92.4; I2 1) and 54.7% (CI 47.6-61.6; I2 81). Pooled rate of therapeutic failures, defined as lack of response to LNSC therapy, was 22.1% (CI 18.3-36.6; I2 74). Post LNSC strictures and perforation pooled rates were 4% and 0.8%, respectively, which are lower than previously reported for RFA. Pooled rate of post procedure abdominal and/or chest pain was 13.6% (CI 11.3-16.3; I2 67). (Table) Conclusion: Our analysis suggests that liquid nitrogen spray cryotherapy is a durable and safe therapeutic modality for BE, in both ablation naïve and experienced patients.Figure 1.: Study analysis Table 1. - Study Outcomes Recurrence Adverse Events Failure F/u Time CE-D (CE-HGD, CE-LGD) CE-IM Dysplasia IM Pain Stricture Perforation Dysphagia Dumot 2009 CE-D 15/ 31 CE-IM 6/ 31 16/25 (LGD 6, HGD/IMCA/ACA, esophagectomy, or death 10) -- 10/31 Mild pain 7/31, severe pain 3/31 3/31 1/31 -- 9/31 12m (6-24) Greenwald 2010 CE-D 22/24 - 15/17 (HGD), 4/4 (ImCA), 3/3 (Barrett’s Carcinoma); CE-HGD - 23/24 CE-IM 13/24 - 9/17 (HGD), 3/4 (ImCA), 1/3 (Barrett’s Carcinoma) -- -- CP 57/323, Abdominal pain 14/323 (procedures) 3/77 1/77 43/323 (procedures) -- 9.3 (3,13) - 13.8 (10,18) Shaheen 2010 CE-D 52/60, CE-HGD 58/60 CE-IM 34/60 -- -- 2/98 3/98 0/98 - -- 10.5m (8.3) [Mean] Halsey 2011 CE-D and CE-HGD 25/36 -- 6/36 5/36 -- -- -- -- 3/36 24m Sengupta 2015 CE-D 12/ 16 CE-IM 5/ 16 after CE-D 0/12 -- -- 3/21 1/21 3/21 -- 7.5m (2-25m) Ghorbani 2016 CE-D 67/80 [HGD: CE-HGD 52/57, CE-D 46/57; LGD: CE-D 21/23] CE-IM 51/80 [HGD: CE-IM 37/57; LGD: CE-IM 14/23] -- -- 28/96. Abdo pain 6/96, CP 22/96 1/96 0/96 11/96 -- 21 m (12–24 m) Suchniak - Mussari 2017 CE-D 17/20 (CE-HGD 14/15, CE-LGD 3/5); CE-ImCA+D - 6/8 CE-IM 16/33 -- -- -- 5/45 0/45 -- 1/15 (with HGD), 2/8 (with ImCA) 27.6m (13.2) [Mean/SD] Ramay 2017 CE-D: 27/36 (CE-HGD 32/39) CE-IM 17/26 after CE-D: 7/39 (HGD) -- -- -- -- -- 13/40 (LGD 3, IM 10) 69.7 (13.8) [53.8-106.0] {Mean/SD} Trindade 2017 CE-D 13/18 (CE-LGD 3/4, CE-HGD 5/7) CE-IM 9/ 18 after CE-D 0/18 after CE-IM 0/18 0/18 0/18 -- -- -- 4.25m (3–11) [Median] Trindade 2018 CE-D 22/27 CE-IM 19/27 -- after CE-IM 9/ 27 0 0 0 0 8/27 (2 LGD, 3 IM, 3 cancer) 2 y [1-5.5] [Median] Thota 2018 CE-D 63/81 CE-IM 33/81 -- after CE-IM 9/63 -- -- -- -- 10/81 31.8m [12.6, 50.7] {Median} Spiceland 2019 CE-D 38/46 CE-IM 21/46 -- -- -- 3/46 -- -- 8/46 (1 cancer, 2 lost f/u, 5 undergoing rx) NR Kaul 2020 CE-D -51/52 CE-IM - 39/52; LGD 6/7; HGD 13/17; T1a 13/17; inv EAC 7/11 4/34 after CE-IM 3/34 0/57 0/57 1/57 0/57 20/39 4.8 yr Fasullo 2021 CE-D 44/62 CE-IM 41/62 6/44 after CE-IM 6/41 0/62 0/62 0/62 -- 11/62 NR