Determining the mechanical properties of cross-laminated timber (CLT) panels is an important issue. A property that is particularly important for CLT used as shear walls in buildings is the in-plane shear modulus. In this study, a method to determine the in-plane shear modulus of 3- and 5-layer CLT panels was developed based on picture frame tests and a correction factor evaluated from finite element simulations. The picture frame test is a biaxial test where a panel is simultaneously compressed and tensioned. Two different testing methods are simulated by finite elements: theoretical pure shear models as a reference cases and picture frame models to simulate the picture frame test setup. An equation for calculating the shear modulus from the measured shear stiffnesses in the picture frame tests is developed by comparisons between tests and finite element simulations of the CLT panels. The results show that pure shear conditions are achieved in the central region of the panels. No influence from the size of the tested panels is observed in the finite element simulations.