Abstract Hereditary inclusion body myopathy (HIBM) is a severe progressive myopathy with onset in adulthood. Weakness begins in the distal muscles but progresses proximally over time, although the quadriceps remains the least affected muscle group. There is no approved treatment. The objective of this study was to quantify muscle weakness and functional limitations to optimize the design of a Phase 2 study of extended-release sialic acid. A convenience sample of subjects concurrently enrolled in a Phase 1 study was recruited to participate in a 1-h test session. Assessments included hand-held dynamometry (HHD), a six-minute walk test (six MWT), gait speed, sit-to-stand and weighted arm lift tests. Twelve subjects (five males, seven females) with a median age of 42 years (30–62) were enrolled. Eleven of 12 subjects required foot drop support with orthotics. HHD was not performed at the ankle as limited motion and profound weakness made valid testing difficult. Of the lower extremity muscle groups tested, the knee extensors were least affected (mean = 54% pred, SD = 11, median = 56%) and the only group testable in all subjects. Knee flexors were the most affected with only four subjects having measurable force. In the upper extremities, gross grip was the most affected (mean = 31% pred, SD = 26, median 25%) followed closely by the shoulder abductors (mean = 38% pred, SD = 11, median = 37%). Mean six MWT distance for the eight subjects able to perform the test was 301 meters (SD = 76) or 42% predicted. Comfortable and maximum gait speeds were 55% (SD = 19) and 44% (SD = 14) predicted, respectively. Only 3 of the 12 subjects were able to rise from a seated position without assistance. Weaker subjects performed fewer repetitions during the 30 s weighted arm lift test. Results suggest that adults with HIBM have profound muscle weakness and impaired function. Assessments appear to be reliable, valid and well tolerated and show promise for use in future trials.