Among individuals with rheumatoid arthritis (RA), stress-associated disease flare can severely impact well-being. Psychological factors such as personal mastery may buffer an individual from the negative effects of those flares. We tested the hypothesis that a high sense of personal mastery would prospectively predict stress reactivity. Measures of pain,perceived stress, fatigue, and mean arterial pressure (MAP) were collected before, during, and after two interpersonal stressors conducted on 73 individuals with RA. Factor analysis of the personal mastery scale yielded two independent factors: a 5-item "fatalism" component and a 2-item "control" component. Individuals with high fatalism scores reported overall greater joint pain at baseline and those scoring high on control exhibited lower MAP, and reported less stress and fatigue at baseline. After controlling for baseline differences, those high in control exhibited greater MAP increase during stress, and less drop in pain when compared to those low in control. These results suggest that individuals high in control may be more susceptible to the effects of acute stress; however, the overall beneficial aspects of high control outweigh the acute negative effects. Personal mastery may play a role in the experience of pain, stress, and fatigue for people with RA.