Abstract Background Inter-observer variability in the Mayo Endoscopic Subscore (MES) for Ulcerative Colitis (UC) is a critical barrier (Kappa∼0.58) (4). While dedicated deep learning (CNN) models are accurate (10), their reliance on massive, fine-tuned datasets (11) creates a significant bottleneck. It remains unknown if general-purpose generative multimodal models can accurately classify the MES in a zero-shot (no training) setting.This proof-of-concept study quantified the diagnostic accuracy and ordinal concordance of a general-purpose multimodal model (Gemini 2.5-Pro) in a strict zero-shot configuration for MES classification, using a public, expert-labelled dataset (12) as the ground truth. Methods This STARD (13) and TRIPOD+AI (14) compliant study used a stratified, random, and balanced sample (N = 200; n = 50 per class, MES 0-3) from the public LIMUC repository (12). The index test was the Gemini 2.5-Pro model, provided with an image and a text prompt containing the official MES criteria, with no prior fine-tuning. The primary outcome was global accuracy. Key secondary outcomes included metrics per class, Mean Absolute Error (MAE), Quadratic Weighted Kappa (QWK) (19) for ordinal concordance, and performance on the clinically critical binary task (inactive/mild MES 0-1 vs. moderate/severe MES 2-3). 95% Confidence Intervals (CIs) were calculated using the Wilson-score method (20, 21) or the BCa bootstrap method (2,000 replicates) (22, 23). Results The model’s overall 4-class accuracy was 72.5% (145/200; 95% CI: 65.9%-78.2%). Ordinal performance was exceptionally strong, achieving a QWK of 0.875 (95% BCa CI: 0.833–0.909), indicating “Near Perfect” agreement (19). The low MAE of 0.29 (95% BCa CI: 0.22–0.36) corroborated this. Error distance analysis showed that 98.5% (197/200) of all predictions were either correct (distance 0) or an adjacent-class error (distance 1). Only 1.5% (n = 3) of errors were of distance 2, and no critical distance 3 errors occurred. For the clinically relevant binary task (MES 0-1 vs. 2-3), the model achieved an accuracy of 0.885 (95% CI: 0.833–0.922), with “Substantial” agreement (Kappa 0.770). Performance was highest at extremes, with 0.920 sensitivity for MES 0 and 0.973 specificity for MES 3. Conclusion This study provides the first evidence that a zero-shot generative multimodal model can classify the MES with “Near Perfect” ordinal concordance, bypassing the fine-tuning bottleneck. This level of ordinal performance suggests that foundation models possess a robust internal visual understanding of mucosal inflammation. 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