Context. For several years, Jupiter-family comets have been the targets of spacecraft missions whose aims are to determine the comets' composition, structure, and physical properties. The Rosetta mission is currently flying towards comet 67P/Churyumov Gerasimenko for a rendezvous in August 2014 and comet 46P/Wirtanen is considered for a rendezvous in 2021 with the PriME (Primitive Material Explorer) mission, which is currently proposed to NASA. Aims. Here we investigate the stability conditions of clathrate hydrates within the comets 67P/Churyumov-Gerasimenko and 46P/Wirtanen by considering an initial mixture of amorphous H 2 O with CO, CO 2 , CH 4 , and H 2 S in the nuclei. Methods. We use a one-dimensional nucleus model, which considers an initially homogeneous sphere composed of a predefined porous mixture of ices and dust in specified proportions and describes heat transmission, gas diffusion, sublimation/recondensation of volatiles within the nucleus, water ice phase transition, dust release, and mantle formation. Results. We show that stability conditions of multiple guest clathrates are permanently reached in the subsurface of both comets, and in a broader manner in the subsurface of all short period comets. The thickness of the stability zone of the clathrate slightly oscillates with time as a function of the heliocentric distance, but never vanishes. When comets approach perihelion, our calculations suggest that clathrate layers, which are located closer to the nucleus surface, may destabilize before amorphous ice is tranformed into crystalline ice.