Stair ascent is a common activity of daily living (ADL), and is often reported to be the most challenging ADL by older adults. The adults who struggle with this task tend to exhibit increasing muscle weakness, decreased balance, fear, and decreased confidence in their ability to navigate stairs. A variety of assistive devices exist to help these individuals ascend stairs, but they tend to have major drawbacks – they have to be installed, are expensive, require arm strength, or present a tripping hazard in a population already prone to tripping. In order to create a portable, inexpensive device to assist in stair ascent, a deeper investigation of stair ascent’s sensitivity to muscle weakness in important muscle groups must be undertaken. We created three-dimensional, muscle-driven simulations of five older healthy subjects ascending stairs and iteratively weakened the peak isometric force of muscles both globally and in major muscle groups to investigate how sensitive stair ascent is to muscle weakness. In general, weakened muscles displayed increased activation and antagonist muscles showed decreased activation. Compensation strategies were often required for bi-articular muscles in order to maintain kinematics and kinetics at all joints. We found that stair ascent is most sensitive to ankle plantar flexor weakness and global weakness. Additionally, the soleus showed the greatest contribution to both support and forward progression for all phases of gait. In comparison to previous studies of gait, our results suggest that stair ascent is more sensitive to global muscle weakness. Simulations appeared to fail when the soleus was too weak to contribute to the ankle plantar flexion moment and other muscles were unable to compensate for soleus weakness. These results suggest that a device targeting the ankle may be beneficial for older adults with muscle weakness, in order to assist with stair ascent. Future studies investigating muscle weakness in this population with different activities of daily living are needed to determine if an ankle assistive device is feasible before design and physical testing can be undertaken.