Supported by a supplement to our Clinical and Translational Science Award, we studied the feasibility of implementing clinical research in Northern Manhattan community practices that primarily serve Hispanic patients. We applied a mixed-methods approach (surveys, focus groups, interviews) based on the PRECEDE-PROCEED model to determine the level of interest in clinical research among community clinicians (both practice-based research network PBRN members and non-PBRN members), the perceived barriers that hamper participation in clinical research, and the perceived facilitators for conducting research in such practices. Survey and qualitative data indicated strong interest in clinical research among current and potential PBRN members if it was relevant to improving quality of care in their practice or community. They also identified important perceived barriers (lack of time, inadequate training in research methods, lack of collaborators and support staff, institutional review board hurdles, and community distrust of research) and the necessary requirements for overcoming barriers to conducting research in busy clinical settings, which included collaborators, mentors, research support staff, and a trusting patient-clinician relationship. It is feasible to conduct clinical research studies in urban community medical practices if the topics are relevant to the community and appropriate enabling structures and processes are put into place.