The Determinants of TB Transmission (DTT) project, a federally-funded study covering the period April 1, 2006-March 31, 2013, and examining the determinants of TB transmission amongst the Canadian-born population (Aboriginal and non-Aboriginal) in the prairie provinces of Canada, took a novel approach to health research involving Aboriginal people. The methodology aligned itself with the recently published Canadian Institutes of Health Research (CIHR) Guidelines for Health Research Involving Aboriginal People and the established principles of Ownership, Control, Access, and Possession (OCAP). This article details the process by which collaboration with Aboriginal peoples was achieved, including the involvement of Aboriginal researchers, the development of Provincial Network Committees (PNCs), and communications with First Nations Chiefs and Council. Strengths of this methodology included Aboriginal organizational and community support with a high rate of participation; PNC leadership, which brought together Aboriginal stakeholders with provincial and federal TB program planners; and the exploration of both on and off-reserve transmission factors. Challenges of the methodology included meeting funding agency timelines and expectations given the gradual process of trust development and PNC-reviewed publication; respecting both community and individual participants' autonomy regarding study participation; and political discomfort with strong Aboriginal involvement. While the methodology required a dedicated investment from researchers and funding agencies alike, the process was worthwhile and achieved a high degree of support from its major collaborators: the Aboriginal peoples.