The purpose of this study was to examine the interactive effects of hormone-replacement therapy (HRT) and physical activity (PA) on the cognitive performance of older women. Postmenopausal women (n = 101) were recruited to complete a PA questionnaire, provide demographic information, and perform the digit-symbol substitution task (DSST) and the trail-making tests (TMT). Regression analyses were conducted for participants with complete data for each cognitive test (DSST n = 62; TMT n = 69). For both tasks, results indicated that PA and education were positively related and age was negatively related to cognitive performance. The interaction of HRT with PA did not add to the predicted variance of either measure of cognitive performance. This was true even after limiting the HRT users to women using unopposed estrogen. It is concluded that the beneficial relationship between PA and these two measures of cognitive performance in postmenopausal women exists irrespective of HRT use.