The zero‐inflated negative binomial regression model (ZINB) is often employed in diverse fields such as dentistry, health care utilization, highway safety, and medicine to examine relationships between exposures of interest and overdispersed count outcomes exhibiting many zeros. The regression coefficients of ZINB have latent class interpretations for a susceptible subpopulation at risk for the disease/condition under study with counts generated from a negative binomial distribution and for a non‐susceptible subpopulation that provides only zero counts. The ZINB parameters, however, are not well‐suited for estimating overall exposure effects, specifically, in quantifying the effect of an explanatory variable in the overall mixture population. In this paper, a marginalized zero‐inflated negative binomial regression (MZINB) model for independent responses is proposed to model the population marginal mean count directly, providing straightforward inference for overall exposure effects based on maximum likelihood estimation. Through simulation studies, the finite sample performance of MZINB is compared with marginalized zero‐inflated Poisson, Poisson, and negative binomial regression. The MZINB model is applied in the evaluation of a school‐based fluoride mouthrinse program on dental caries in 677 children. Copyright © 2015 John Wiley & Sons, Ltd.