Academic procrastination has been a widespread problem behavior among undergraduates. This study aimed to examine the prevalence of academic procrastination among undergraduates in health professions, and explore the mediation effects of self-efficacy for self-regulation and fear of failure in the relationship between self-esteem and academic procrastination. A cross-sectional design was used to study 1184 undergraduates in health professions from China. Participants completed measures of academic procrastination, self-esteem, self-efficacy for self-regulation and fear of failure. We used Pearson product-moment correlation to examine the bivariate correlations between study variables, and path analysis to examine mediation. Among the 1184 undergraduates, 877 (74.1%) procrastinated on at least one type of academic task. The total score for academic procrastination was negatively correlated with scores for self-esteem and self-efficacy for self-regulation, and positively correlated with the score for fear of failure. Moreover, the relationship between self-esteem and academic procrastination was fully mediated by self-efficacy for self-regulation (indirect effect: ß = - .15, 95% bootstrap CI - .19 to - .11) and fear of failure (indirect effect: ß = - .06, 95% bootstrap CI - .09 to - .04). These findings suggest that interventions targeting the enhancement of self-efficacy for self-regulation and the conquest of fear of failure may prevent or reduce academic procrastination among undergraduates in health professions, especially for those with lower self-esteem.