Introduction: Liquid nitrogen spray cryotherapy (SCT) is used for endoscopic ablation of multiple diseases including Barrett's esophagus (BE) and esophageal cancer (EC). SCT does not involve the tissue contact or mechanical debridement required with radiofrequency ablation (RFA). Therefore, there is a theoretical advantage to SCT over RFA in patients on blood thinners, as mucosal trauma could increase the risk of significant bleeding. Our aim was to assess whether blood thinner use at the time of SCT affects blood loss. Methods: All patients who received SCT for BE or EC by a single high-volume specialist between May 2009 and May 2015 were included. Medication lists were reviewed and patients on anti-platelet agents less than 5 days before SCT or anti-coagulants less than 3 days before the procedure were considered active users. Minimal estimated blood loss (EBL) was defined as up to 10 mL. Demographic, histologic and endoscopic data were aggregated and de-identified prior to analysis. Results: A total of 215 SCT procedures were performed on 55 patients (75% male, mean age 68 years), 152 for BE and 63 for EC. Just over half (115) were performed on 35 patients who did not take blood thinners on a regular basis. Another 44 procedures (20%) were performed on 13 patients whose blood thinners were held. The remaining 56 procedures (26%) were performed on 19 patients actively taking blood thinners at the time of SCT. In the single case with an EBL over 10 mL, EC was treated with no history of blood thinner use. Only 44 cases had an EBL of 6-10 mL, of which 32 were performed for EC and 12 for BE. Blood thinners were not actively prescribed or were held appropriately for 27 procedures (61%) with 6-10 mL of EBL. Overall, both for cases with active blood thinner use and for held blood thinners, EBL was 1-5 mL in 70% of cases and 6-10 mL in 30% of cases, compared to 88% and 12% respectively without blood thinner use. Conclusion: These data demonstrate excessive blood loss from SCT is very rare. Active or recent use of anti-platelet agents or anti-coagulants may result in a slightly higher EBL that is unlikely to be hemodynamically significant. Increased EBL seems to be related to diagnosis, with more bleeding in cancer cases. Regardless of diagnosis, SCT appears to be a safe treatment option with respect to bleeding for patients who are unable to discontinue blood thinner use prior to endoscopy. It also appears unnecessary to hold these medications for SCT to avoid significant blood loss.