Objective Assess the effects of long-duration microgravity and gravitational transitions on fine motor skills using a tablet-based test battery of four fine motor tasks: Pointing, Dragging, Shape Tracing, and Pinch-Rotate. Background While there have been some studies on fine motor skills in microgravity, few have measured the fine motor skills that are core components of interaction with computer-based devices, and none have measured performance systematically, to include preflight, inflight, and postflight space mission time periods. Methods Seven astronauts completed the Fine Motor Skills test battery 30–40 times before, during, and up to 30 days after standard duration International Space Station missions, while a matching set of seven ground-based control participants also completed the battery over a comparable period of time. Response time and accuracy were the primary outcome measures. Results Relative to controls, astronauts experienced fine motor skill decrements at gravitational transitions (first week on orbit, and first month post landing). No decrements were found inflight after the first week of adaptation. Conclusion Gravitational transitions appear to negatively impact fine motor skills needed to operate small controls with accuracy, such as those on touchscreen interfaces. This raises concerns for future long-duration crewmembers who will land on a planetary surface and need to perform critical tasks accurately, such as configuring spacesuits, powering up a habitat, or teleoperating rovers. Application Results from this study highlight the need for confirmatory research, and the possible need for countermeasure development. The Fine Motor Skills test battery may have application outside of NASA as a fine motor skills diagnostic screening, rehabilitation, or readiness-to-perform tool.