With the aim of understanding failure modes in the peeling of silicone-based adhesive joints and, in particular, the occurrence of adhesive or cohesive failure, an experimental campaign has been conducted by considering plastic substrates with different surface roughness. A flexible strip has been bonded onto such substrates using a silicone adhesive, by controlling its thickness. Peeling tests with 90º and 180º peeling angle configurations have been performed and the effect of joint parameters, such as surface roughness and adhesive thickness, onto the adhesion energy and the failure mode are herein discussed in detail. Experimental results show that the failure mode varies in each peeling test configuration such that in the case of 180º peeling test there is mainly cohesive failure, while for 90º peeling angle, a combination of adhesive and cohesive failure occurs. Moreover, due to the presence of different failure modes in each peeling configuration, the substrate roughness can increase the adhesion energy only in 90º peeling tests.