Background: The biomechanics of the gastrointestinal tract strongly influence food disintegration and digestion in vivo. Most currently available in vitro dynamic digestion models lack, however, the ability of mimicking the oro-gastrointestinal morphology and contractions, possibly overlooking the effect of mechanical forces in the digestive process. Methods: We investigated the operation of a biomechanically-relevant digestion simulator equipped with a silicon real-size model of the human stomach (dynamic in vitro human stomach system, DHS-IV) using dairy food matrices (liquid, semisolid and solid). The system mimics morphology, anatomical structures and biochemical environments of oesophagus and gastrointestinal tract present in vivo in adult humans. A set of precisely controlled rollers mimics the dynamic aspects and peristaltic contractions. Results: We reproduced the gastric emptying curves and gastric digestion conditions for different food matrices observed in vivo, recreating human chewing and ingestion rates. We describe here the key structure and functioning of the digestor, the operational parameters that influence mostly the gastric emptying rate, and the adjustments that have shown to be necessary to control gastric emptying and digestion parameters. Conclusions: The biomechanically-relevant in vitro digestion system (DHS-IV) can provide an effective approach for studying the structural and physicochemical changes during digestion in the stomach