There is considerable debate about the feasibility and appropriateness of research in dental primary care, particularly the conduct of clinical trials compared with other research designs. While an evidence-based approach to clinical practice is advocated to improve patient care, research relevant to primary care is sparse, with a gap between research findings and clinical practice. Conducting research in a primary care setting is important, while recruitment and retention methods are crucial for generalizability of the results. Systematic reviews show that high-quality trials provide more reliable outcomes, due to methods such as concealment of allocation to groups, blinding, and particularly outcome assessment and loss to follow-up. Our experience of clinical trials in general dental practice has given insight into the design and conduct that ensure feasibility and generalizability. However, only with adequate funding, good infrastructure, and networks can research be conducted in dental primary care.