The index of refraction (n) of materials and/or tissues depends on their physical properties and serves as a source of optical contrast in imaging. The variations of the index of refraction have also been investigated for diagnostic purposes in various fields, such as hematology, oncology, etc., since they can signify disease and cell dynamic changes. Optical coherence tomography (OCT) has been used in the past to measure the index ex vivo. However, most methodologies described in the literature are not appropriate for in vivo imaging since they require either a mirror below the sample or a complicated imaging setup and algorithms. We describe a technique that uses two images, obtained at different angles, to estimate the index of refraction and can, thus, also be applied in vivo. The index of refraction is calculated from the path-length difference observed by the OCT beam at the two different angles. When a reflector is not available, the path-length difference can be estimated using image registration and the cross-correlation of adjacent A-scans. The proposed technique was validated experimentally using both clear and scattering samples. The resulting values of the index of refraction were within ∼1  %   of the expected. The main limitation of this technique is the effect of misalignment on the results, requiring the precision provided by an angular-resolved OCT system. These very promising results provide evidence that the dual-angle method should be further investigated and validated on human tissues so that it can be developed into a clinically useful diagnostic tool in the future.