Patient comfort is often assessed during gastrointestinal procedures to guide sedation. There are, however, no validated scales appropriate for routine comfort assessment. This study validated a single-item La Crosse (WI) intra-endoscopy sedation comfort score (L-WISC) by determining interobserver agreement and correlation with patient outcomes. The study was conducted in prospective outpatient cohorts of patients undergoing outpatient esophagogastroduodenoscopy and/or colonoscopy at a regional healthcare medical center endoscopy unit. In Phase 1, independent assessments of 100 patients' intraprocedural comfort by the endoscopist and nurse determined interobserver agreement. In Phase 2, nurses assessed 200 patients, who were provided surveys to self-report their comfort 2 weeks postprocedure. In Phase 1, there was fair interobserver agreement (weighted κ = 0.36, with 95% confidence intervals [CI] [0.19, 0.53]). After L-WISC revisions, Phase 1 was repeated with moderate agreement (weighted κ = 0.45; 95% CI [0.31, 0.60]). In Phase 2, using the revised score, there was poor agreement (weighted κ = 0.098; 95% CI [-0.0020, 0.20]) between nurses' and patients' scores. The L-WISC is the first intraprocedural gastrointestinal comfort score appropriate for routine use to be validated with interobserver agreement and correlation with patient outcomes. It has reproducibility between endoscopists and nurses. It does not predict patient recollection of sedation comfort, but it remains unclear whether such prediction is possible with the use of amnestic sedatives. The L-WISC provides standardized levels of patient comfort to guide sedation titration routinely during outpatient endoscopy.