In this work, the complex refractive indexes of seven PEDOT:PSS samples, three with isotropic behavior and four with optical anisotropy, were determined. For the anisotropic samples, the ordinary and extraordinary components of the refractive index were described. The effect of the film thickness, measurement technique and preparation method on the extinction coefficient (k) and refractive index (n) of each sample was also discussed. Important differences (up to 20% in the average n) were found among the samples investigated. In most anisotropic films, the mean value of the extraordinary component was between 7 and 10% higher than that of the ordinary. In the three isotropic films, the average k rose when the film thickness increased. Moreover, the different sets of refractive index data were fitted to three different models: the original Forouhi–Bloomer model, the Liu (2007) model and the revised version of the Forouhi–Bloomer model (2019). In general, Liu’s model gave better results, with small errors in n and k (<7.81 and 4.68%, respectively, in all the cases). However, this model had seven fitting parameters, which led to significantly longer computation time than the other two models. The influence of the differences in the measurement of the complex refractive index on the simulation of the optical properties of PEDOT:PSS multilayers was discussed. The results showed that n must be known precisely to accurately calculate the light absorption in a multilayer, without ignoring the isotropic or anisotropic behavior of the material or the influence of the layer thickness on its optical properties. This study aids in the development of simulation and optimization tools that allow understanding the optical properties of PEDOT:PSS films for their potential applications in organic optoelectronic devices, such as organic solar cells.