The penetration depth of optical microscopy in biological tissue is limited by attenuation due to absorption and scattering. Scattering decreases with wavelength, while water absorption is locally minimized at so-called infrared “optical windows.” Of the four infrared optical windows, light in the longest wavelength window at 2200 nm experiences the least scattering and the most water absorption. Therefore, the 2200 nm window is rarely used for biological microscopy. However, fractional water content differs greatly between tissues. Therefore, the best optical window for deep imaging may depend on tissue type. Here, we demonstrate the benefits of the 2200 nm optical window for imaging through the skull, which is highly turbid with a relatively low water content. A spectral domain optical coherence tomography (OCT) system at ~2200 nm was built. A maximum sensitivity of 86 dB and a tissue axial resolution of 13.9 µm were achieved. To assess relative contributions of scattering and water absorption, 2200 nm was compared with 1300 nm. In vivo cortical vasculature was imaged angiographically through the intact skull in mice. Overall 2200 nm experienced less attenuation through the intact skull. In cortical layer I, 1300 nm, which experiences more scattering but less water absorption, and 2200 nm, which experiences less scattering but more water absorption, exhibit similar attenuation. In deeper cortical layer II/III, higher attenuation was observed at 2200 nm due to higher water absorption. Thus the infrared window at 2200 nm may provide advantages for imaging layers at or near the cortical surface through thick skull.