We investigated the optimal operational conditions for utilizing a broadband supercontinuum (SC) source in a portable 800 nm spectral-domain (SD) endoscopic OCT system to enable high resolution, high-sensitivity, and high-speed imaging in vivo. A SC source with a 3-dB bandwidth of ∼246 nm was employed to obtain an axial resolution of ∼2.7 μm (in air) and an optimal detection sensitivity of ∼-107 dB with an imaging speed up to 35 frames/s (at 70 k A-scans/s). The performance of the SC-based SD-OCT endoscopy system was demonstrated by imaging guinea pig esophagus in vivo, achieving image quality comparable to that acquired with a broadband home-built Ti:sapphire laser.