Brief motivational intervention (bMI) is a therapeutic approach that encourages self‐efficacy and may have a positive effect on breastfeeding self‐efficacy (BSE). The purpose of this study was to analyze the effectiveness of a bMI in increasing BSE in women who started breastfeeding in the immediate postpartum period and to explore the roles of general self‐efficacy and other baseline variables in this relationship. A randomized, parallel‐group clinical trial was carried out. A bMI was compared with an educational session on breastfeeding. Changes in BSE and its dimensions and the interaction and mediation/moderation of general self‐efficacy and other variables were analyzed. BSE increased in the bMI group from a mean baseline score of 59.14 (±9.35) to 64.62 (±7.91) at 1st month (p < 0.001). An interaction was found in that only women with higher education had an improvement in BSE during the follow‐up period that was attributable to the bMI (mean difference between the bMI and the attention control group: 18.25 (95% confidence interval: 5.86–30.19; p = 0.006). This interaction was not found for the changes produced in the intrapersonal thoughts dimension of BSE, whose scores were higher in the bMI group at 3 and 6 months. General self‐efficacy exerted a moderating effect on the association of bMI with BSE change. The effect of bMI was no longer significant when the general self‐efficacy score was above 84. Thus, bMI is effective in increasing BSE. This effectiveness was limited by the mother's educational level and moderated by baseline general self‐efficacy.