Internal explosions caused by gas leaks are very common phenomena in this time and can lead to structural failures seriously compromising the static of a building, both in civil and industrial structures, and in some cases can involve the consequent entire structure’ failure. The main purpose of this study is to numerically reproduce the damage effects caused by a vented explosion in a multi-storey framed reinforced concrete structure with masonry infill walls. Gas-leakage has been supposed to be situated in one room, generally that used as a kitchen. ANSYS AUTODYN® has been used to manage both the structural (Lagrangian solver) and the fluid-dynamic (Eulerian solver) issues and to make feasible their interactions. Reinforced concrete and masonry were implemented as homogenized materials and increased materials’ resistances due to high strain rates were considered through the DIF coefficients. The analysis focuses on the gas mixture usually used for domestic purposes mainly consisting of methane (80% v/v) and completed by ethane, propane and n-butane. A thermodynamic and stoichiometric chemical analysis allowed for the estimation of the main parameters involved in the explosion. Results show that such a mixture has the capability to release a specific energy amounting to about 46,800 kJ/kg, theoretically exceeding that of the TNT by approximately 10 times. Finally the pressure caused by the blast wave on the walls has been evaluated.