The integration of original data from multiple antiretroviral (ARV) adherence studies offers a promising, but little used method to generate evidence to advance the field. This paper provides an overview of the design and implementation of MACH14, a collaborative, multi-site study in which a large data system has been created for integrated analyses by pooling original data from 16 longitudinal ARV adherence studies. Studies selected met specific criteria including similar research design and data domains such as adherence measured with medication event monitoring system, psychosocial factors related to adherence behavior, and virologic and clinical outcomes. The data system created contains individual data (collected between 1997 and 2009) from 2,860 HIV patients. Collaboration helped resolve the challenges inherent in pooling data across multiple studies, yet produced a data system with strong statistical power and potentially greater capacity to address key scientific questions than possible with single-sample studies or even meta-analytic designs.