Background Mobile health (mHealth) video interventions are often transferred across settings. Although the outcomes of these transferred interventions are frequently published, the process of adapting such videos is less described, particularly within and across lower-income contexts. This study fills a gap in the literature by outlining experiences and priorities adapting a suite of South African maternal nutrition videos to the context of rural Burkina Faso. Objective The objective of this study was to determine the key components in adapting a suite of maternal nutrition mHealth videos across settings. Methods Guided by the principles of human-centered design, this qualitative study included 10 focus group discussions, 30 in-depth interviews, and 30 observations. We first used focus group discussions to capture insights on local nutrition and impressions of the original (South African) videos. After making rapid adjustments based on these focus group discussions, we used additional methods (focus group discussions, in-depth interviews, and observations) to identify challenges, essential video refinements, and preferences in terms of content delivery. All data were collected in French or Dioula, recorded, transcribed, and translated as necessary into French before being thematically coded by two authors. Results We propose a 3-pronged Video Adaptation Framework that places the aim of video adaptation at the center of a triangle framed by end recipients, health workers, and the environment. End recipients (here, pregnant or lactating mothers) directed us to (1) align the appearance, priorities, and practices of the video’s protagonist to those of Burkinabe women; (2) be mindful of local realities whether economic, health-related, or educational; and (3) identify and routinely reiterate key points throughout videos and via reminder cards. Health workers (here, Community Health Workers and Mentor Mothers delivering the videos) guided us to (1) improve technology training, (2) simplify language and images, and (3) increase the frequency of their engagements with end recipients. In terms of the environment, respondents guided us to localize climate, vegetation, diction, and how foods are depicted. Conclusions Design research provided valuable insights in terms of developing a framework for video adaptation across settings, which other interventionists and scholars can use to guide adaptations of similar interventions.