Abstract Introduction Leprosy is a chronic infectious disease, caused by Mycobacterium leprae , which is endemic in some tropical countries. It is necessary to implement strategies for its detection and elimination. We propose a strategy useful could be identifying risk factors associated with a seropositive test in leprosy. Objective We aimed to quantify the infection rates and identify risk factors for M. leprae infection using the serological evaluations against NDO-LID in family clusters of leprosy patients, from regions with a high burden of leprosy in Colombia. Results We observed that belong to a low socioeconomic condition (OR 5.6 [95% IC 1.1-29]) and living in geographic area of residing such as Chocó and Atlántico (OR 2 [95% IC 1.1-3.7]) could be risk factors related to infection by M. leprae between the members of a family cluster. Conclusions Leprosy is a persistent disease that affects vulnerable and large family clusters, in which the detection of antibodies against NDO-LID can be a useful tool for early detection of M. leprae in family clusters with high risk for this infection.