Early diagnosis of esophageal cancer can be enhanced by the application of optical coherence tomography (OCT) to gastrointestinal endoscopy. One of the most salient examples is the use of OCT to augment the detection of dysplasia during Barrett's esophagus (BE) surveillance, the established precursor to esophageal adenocarcinoma (EAC). 1 Reid BJ Li X Galipeau PC et al. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010; 10: 87-101https://doi.org/10.1038/nrc2773 Crossref PubMed Scopus (303) Google Scholar , 2 Pohl H Welch HG The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005; 97: 142-146https://doi.org/10.1093/jnci/dji024 Crossref PubMed Scopus (1069) Google Scholar A previously commercially available balloon-based imaging catheter system, also known as volumetric laser endomicroscopy (VLE), was designed to provide circumferential esophageal imaging at the time of endoscopy. The VLE system uses a 1300 nm wavelength-swept laser and provides images with an axial resolution of 7 µm up to a depth of 3 mm. VLE is capable of resolving microarchitectural features associated with early neoplasia in BE including irregular glandular morphology and increased surface signal intensity. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Scoring systems that incorporate these features are associated with a sensitivity of 76-83% and specificity of 71-79% in the diagnosis of BE neoplasia. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar , 4 Swager AF Tearney GJ Leggett CL et al. Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett’s esophagus using high-quality histological correlation. Gastrointest Endosc. 2017; 85: 918-926.e7https://doi.org/10.1016/j.gie.2016.09.012 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Similarly, esophageal OCT has been used in the diagnosis and staging of squamous cell carcinoma (ESCC) where layer effacement predicts the depth of invasion. 5 Trindade AJ Benias PC Inamdar S et al. Use of volumetric laser endomicroscopy for determining candidates for endoscopic therapy in superficial esophageal squamous cell carcinoma. United European Gastroenterol J. 2018; 6: 838-845https://doi.org/10.1177/2050640618761701 Crossref PubMed Scopus (5) Google Scholar In the last decade, ultra-high resolution (UHR) OCT systems that operate at 800 nm and achieve an axial resolution closer to 2.5 µm have been developed. Our group previously described a super-achromatic OCT capsule designed for UHR esophageal imaging. 6 Li K Liang W Mavadia-Shukla J et al. Super-achromatic optical coherence tomography capsule for ultrahigh-resolution imaging of esophagus. J Biophotonics. 2019; 12e201800205https://doi.org/10.1002/jbio.201800205 Crossref PubMed Scopus (16) Google Scholar In the present study, we compare the imaging capability of UHR OCT to VLE in distinguishing microarchitectural features associated with esophageal neoplasia by imaging ex vivo esophageal resection specimens obtained from patients undergoing clinical endoscopy.