Objective Treatment-emergent side effects are frequent events, particularly during the uptitration of antiepileptic drugs. So far, monitoring of such adverse events in outpatients has often been limited to intervals of weeks or months. We here report the application of a new device for temporally fine-grained assessment of objective well-being and cognitive performance using personal digital assistants (PDAs). Methods Twenty adult patients with epilepsy participated in this pilot study. Ten received add-on treatment with levetiracetam. Ten patients with constant medication served as a control group. Differences between groups with respect to self-rated cognitive condition, psychophysical condition, aggressiveness, and cognitive test performance in a concentration test assessed three times daily (morning, early afternoon, and evening), over the course of 6 days, were analyzed. Results Levetiracetam-treated patients manifested an early augmentation of self-rated aggressiveness, which increased in intensity over the course of days. Aggressiveness reached a maximum in the early afternoon across days. There were no major changes in cognitive performance, except for an increase in morning performance in the control group. Conclusions This study demonstrates the feasibility of a new method of ambulatory assessment of behavioral and cognitive data during titration of antiepileptic drugs. Significant changes in aggressiveness under add-on treatment with levetiracetam were found to be dependent on the time of assessment during the day. These results suggest that PDA-based ambulatory monitoring of patients with epilepsy may be a promising tool for early detection of drug-related side effects and, thus, may constitute a significant improvement in patient care.