Objective To explore the effects of testosterone on cognitive performance in healthy postmenopausal women. Study design Open-label pilot study. Nine postmenopausal women on non-oral hormone replacement therapy, aged 47–60 years received transdermal testosterone spray for 26 weeks. A control group of 30 women provided normative data for comparison. Main outcome measures Scores from a computerized cognitive test battery performed pre- and post treatment, at 0 and 26 weeks. Results There were no differences between treatment/normative groups in any parameter at baseline. At week 26 scores for the International Shopping list task including delayed recall (verbal learning and memory) and the continuous paired associate learning task (visual learning and memory) were significantly higher in the treatment group as compared to the normative group (p <0.05). Significant improvements from baseline were observed for the International Shopping list delayed recall (verbal learning and memory) and Groton Maze recall tasks (visual learning and memory) for the treatment group (both p <0.05), after 26 weeks. There were no significant differences between baseline and week 26 in the normative group. In the regression analysis which modeled the score at week 26, and which included a bootstrapping approach, the beta coefficient for the treatment group was statistically significant when age and baseline score were taken into account for the International Shopping list task including delayed recall (both p <0.02). Conclusion Testosterone improved cognitive performance in the domain of verbal learning and memory in a pilot study of healthy postmenopausal women and is worthy of further exploration in a randomized placebo controlled study.