Preventing non-adherence and treating adherence failure are important to consider in designing community-based clinical trials. The approach and methods for managing adherence are vital. This paper describes a practical and theoretically-based strategy for managing adherence in a small cancer prevention trial with subjects (n = 40) taking a non-steroidal anti-inflammatory drug, piroxicam. Average daily pill intake adherence was exceptionally high (97.4%) as measured by self-report calendar. Thus, the generalized adherence enhancement approach used in this study may have been a related factor, although statistical model-testing was not possible in this small trial. The generalized intervention took into account factors such as the potential barriers and benefits of being in the study, self-efficacy and satisfaction with the participant/staff relationship. These and other theoretical variables were incorporated into an overall adherence strategy that is discussed.