Web-based tailored approaches hold much promise as effective means for delivering health education and improving public health. This study examines the effects of interactive tailored health videos on attention to health messages using neurophysiological changes measured by Electroencephalogram (EEG) and Electrocardiogram (EKG). Sixty-eight college students were randomized to examine one of two conditions: an interactive tailored health video using web-automated human interaction technology or a static site on the same health topic. Neurophysiological changes during exposure to stimuli were measured using event-related potentials (ERP) related toP300 and N1, as well as heart rate variability (HRV), including low-frequency power (LF), high-frequency power (HF), and the LF/HF ratio measurements. A survey questionnaire examined participants’ self-reported perceptions about their viewing experience including: attention, interactivity, overall evaluation, preference, and engagement. Results show that the P300 and HF values were significantly higher when viewing the WAHI compared to when viewing the static site, indicating greater levels of attention, which was confirmed by the self-reported data. These results suggested that interactive tailored health intervention programs achieved a relatively greater effect on attention levels indicated by ERP, HRV and self-report, when compared to static message delivery. The study indicated that further research should investigate other neurophysiologic analyses as possible means to better assess the impact of interactive tailored video as a health education approach.