Purpose: Endoscopic liquid nitrogen spray cryotherapy has been used for management of dysplastic Barrett's esophagus and also early esophageal cancer. Use of cryotherapy in patients with surgically altered gastric anatomy is a relative contra-indication due to the potential risk of gastrointestinal perforation from expansion of liquid nitrogen and has not been previously reported. Aim: To assess the feasibility and complications of endoscopic spray cryotherapy in patients with post-surgical gastric anatomy. Methods: Our electronic endoscopy databases were used to identify patients with surgically altered gastric anatomy who underwent liquid nitrogen endoscopic spray cryotherapy (CryoSpray Ablation System, CSA Medical, Baltimore, MD). Medical records were reviewed to collect data including procedure indication, post-operative anatomy, therapy time/number of freeze-thaw cycles, number of sessions, follow up period, outcomes and complications. Results: 41 endoscopic cryotherapy procedures were performed in 8 patients with altered foregut anatomy (mean age 69 years, range 44-82; 63% male). 4 patients (50%) had Barrett's esophagus with high grade dysplasia, 1 had esophageal adenocarcinoma, 1 had gastric adenocarcinoma at the gastrojejunal anastomosis, 1 had gastric high grade dysplasia, and 1 had non-dysplastic Barrett's. Post-surgical anatomy included 3 patients with Whipple anatomy, and 1 each with RY gastric bypass, sleeve gastrectomy, fundoplication, Billroth II anatomy, and partial esophagectomy/gastrectomy. The decompression tube was placed in the stomach in 6/8 (75%) patients and in the jejunum in 2/8 patients (25%). 10-20 second freeze-thaw cycles (mean 16.6 seconds/cycle; 3.3 cycles/session, range 2-6) were performed. An average of 5.1 sessions were performed per patient (range 2-14). Mean follow-up time was 16.4 months (range 2-60). Outcomes included complete Barrett's ablation (normal squamous epithelium) in 1, downgrading of gastric high grade to low grade dysplasia in 1, downgrading of high grade dysplasia to non-dysplastic Barrett's in 2, marked reduction in tumor size in 1 (palliative therapy only), reduction in visible Barrett's segment in 2, and no endoscopic change in 1 patient (no prior visible lesion in this patient but pathology had been positive for cancer; therapy ongoing). There were no perforations noted. 2/8 patients (25%) had mild non-cardiac chest pain after cryotherapy. Conclusion: Endoscopic liquid nitrogen spray cryotherapy may be safely used in patients with post-surgical gastric anatomy. Careful placement of the decompression tube remains important.