Background: The NIH Toolbox - Cognition Battery (NIHTB-CB) is a computerized cognitive assessment designed for clinical research that is administered in-person. Here, we explored the feasibility and validity of a novel video-conference protocol for administering the NIHTB-CB. Since our protocol required repeated assessments, we further explored the NIHTB-CB’s practice effect. Methods: Twenty-five healthy participants completed the NIHTB-CB under two separate conditions four weeks apart. The standard condition followed the recommended administration protocol, whereas the video-conference condition had the examiner and participant in separate rooms but able to communicate over video-conference. A linear mixed-model analysis was performed to explore the fixed effect of testing condition and time on NIHTB-CB performance. Results: Across all three NIHTB-CB composite scores (total, fluid and crystallized cognition) no significant fixed effect of administration condition was found. A significant practice effect was observed for the fluid and total cognition composite scores over a 29.0 (± 2.1) day test-retest interval. Conclusions: Our novel video-conference protocol for the NIHTB-CB is equivalent to the standard protocol in healthy participants, and may provide a solution for researchers seeking to engage study participants at remote sites. If the NIHTB-CB is used longitudinally to monitor patients, corrections for repeated measures may be required.