Very limited operational research (OR) emerges from programme settings in low-income countries where the greatest burden of disease lies. The price paid for this void includes a lack of understanding of how health systems are actually functioning, not knowing what works and what does not, and an inability to propose adapted and innovative solutions to programme problems. We use the National Tuberculosis Control Programme as an example to advocate for strong programme-level leadership to steer OR and build viable relationships between programme managers, researchers and policy makers. We highlight the need to create a stimulating environment for conducting OR and identify some of the main practical challenges and enabling factors at programme level. We focus on the important role of an OR focal point within programmes and practical approaches to training that can deliver timely and quantifiable outputs. Finally, we emphasise the need to measure successful OR leadership development at programme level and we propose parameters by which this can be assessed. This paper 1) provides reasons why programmes should take the lead in coordinating and directing OR, 2) identifies the practical challenges and enabling factors for implementing, managing and sustaining OR and 3) proposes parameters for measuring successful leadership capacity development in OR.