Background: Bubbles often mask the mucosa during capsule endoscopy (CE). Clinical scores assessing the cleanliness and the amount of bubbles in the small bowel (SB) are poorly reproducible unlike machine learning (ML) solutions. We aimed to measure the amount of bubbles with ML algorithms in SB CE recordings, and compare two polyethylene glycol (PEG)-based preparations, with and without simethicone, in patients with obscure gastro-intestinal bleeding (OGIB). Patients & Methods: All consecutive outpatients with OGIB from a tertiary care center received a PEG-based preparation, without or with simethicone, in two different periods. The primary outcome was a difference in the proportions (%) of frames with abundant bubbles (>10%) along the full-length video sequences between the two periods. SB CE recordings were analyzed by a validated computed algorithm based on a grey-level of co-occurrence matrix (GLCM), to assess the abundance of bubbles in each frame. Results: In total, 105 third generation SB CE recordings were analyzed (48 without simethicone and 57 with simethicone-added preparations). A significant association was shown between the use of a simethicone-added preparation and a lower abundance of bubbles along the SB (p = 0.04). A significantly lower proportion of “abundant in bubbles” frames was observed in the fourth quartile (30.5% vs. 20.6%, p = 0.02). There was no significant impact of the use of simethicone in terms of diagnostic yield, SB transit time and completion rate. Conclusion: An accurate and reproducible computed algorithm demonstrated significant decrease in the abundance of bubbles along SB CE recordings, with a marked effect in the last quartile, in patients for whom simethicone had been added in PEG-based preparations, compared to those without simethicone