In preparation for an electronic mail (e-mail) and web-based health promotion intervention across multiple worksites, secure, regulatory-compliant, user-friendly e-mail and Internet applications were used to recruit potential participants across worksites, to enroll participants, and to collect baseline health assessment data. Specific hardware and software information technology environments were required of the 19 participating worksites. Sequential e-mails introduced the study and invited participation. Twenty-four percent of all employees (1106 of approximately 4600) provided consent. E-mail delivered a web link for the baseline study assessment, and reminder e-mails were sent to prompt completion. Of those who consented, 888 (80%) completed baseline health and behavior data surveys. An HTML-native web survey software was more stable across computing environments. Using e-mail and web assessment, this research recruited, enrolled, and collected data from more than 850 participants. Technical and operational challenges emerged at each step. Solutions and recommendations are discussed. Overall, this experience suggests that the use of e-mail and web software can facilitate recruitment, enrollment, and data acquisition through direct contact with study participants. This experience yields a series of lessons learned for using e-mail and the Internet to support multi-site trials.