In-vivo skin characterization methods were shown to be useful in detection of microstructural alterations of the dermis due to skin diseases. Specifically the diagnostic potential of skin suction has been widely explored, yet measurement uncertainties prevented so far its application in clinical assessment. In the present work, we analyse specific factors influencing the reliability of suction measurements. We recently proposed a novel suction device, called Nimble, addressing the limitations of existing instruments, and applied it in clinical trials quantifying mechanical differences between healthy skin and scars. Measurements were performed with the commercial device Cutometer and with the new device. A set of new suction measurements was carried out on scar tissue and healthy skin and FE-based inverse analysis was applied to determine corresponding parameters of a hyperelastic-viscoelastic material model. FE simulations were used to rationalize differences between suction protocols and to analyse specific factors influencing the measurement procedure. Tissue stiffness obtained from Cutometer measurements was significantly higher compared to the one from Nimble measurements, which was shown to be associated with the higher deformation levels in the Cutometer and the non-linear mechanical response of skin. The effect of the contact force exerted on skin during suction measurements was quantified, along with an analysis of the effectiveness of a corresponding correction procedure. Parametric studies demonstrated the inherently higher sensitivity of displacement- over load-controlled suction measurements, thus rationalizing the superior ability of the Nimble to distinguish between tissues.