In an Anaerobic Digestion (AD) process treating particulate substrates, the size of solids is expected to negatively affect the rate of hydrolysis step and consequently influence the performance of the whole process. To avoid any disadvantage due to size of solids, expensive pre-treatments aimed at disintegrating and solubilizing substrates are commonly conducted prior to AD. This practice is doubtlessly successful, but not always necessary, since some organic substrates, although particulate, once immersed in water, tend to solubilize immediately. This aspect, if properly considered, could result in saving money and time in the AD process, as well as refining the development and calibration of AD mathematical models. The present study is actually aimed at demonstrating, through experiments and mathematical simulations, different results deriving from the AD process performed, under the same operating conditions, on two different substrates, i.e. homemade pasta and carrot batons, having the same particle size, but different chemical composition and texture. Experimental outcomes highlighted the effect of particles size on bio-methane production only from the bio-methanation potential tests (BMP) conducted on carrot batons. Similar results were obtained by mathematical model calibration, i.e., different kinetic constants for differently-sized carrot batons and same kinetic constant for differently-sized homemade pasta solids.