Understanding work ability, with the goal of promoting it, is important for individuals as well as organizations. It is especially important to study work ability in health care workers, who face many work-related challenges that may threaten work ability. We studied various job demands, job resources, and interactions of demands and resources relating to work ability using the Job Demands–Resources model as a framework. Acute care health care workers from six nations (US, Australia, UK, Brazil, Croatia, and Poland) completed a survey. Role demands related to work ability in the Australia sample only, and supervisor support related to work ability in the Australia sample only. Yet, high levels of supervisor support significantly moderated (buffered) negative relationships between physical demands and work ability in the US sample, along with negative relationships between role demands and work ability in both the Croatia and UK samples. Skill discretion related to work ability in every nation sample, and therefore appears to be particularly important to work ability perceptions. In addition, skill discretion moderated (buffered) a negative relationship between role demands and work ability in the Australia sample. We therefore recommend that interventions to help preserve or improve work ability target this important job resource.