Introduction Epigenetic mechanisms regulating the level of BDNF gene expression correlate with achieving remission in the course of Major Depressive Disorder in adults. Studies in this area may contribute to individualization of antidepressant pharmacotherapy and increasing its effectiveness, but the amount of data on this subject in the pediatric population is limited. To date, no study has prospectively investigated changes in the BDNF gene methylation level following antidepressant treatment in adolescents. Aim Therefore, we aimed to examine the BDNF gene exon IV promoter methylation status in the group of adolescents treated for the first-lifetime depressive episode. Moreover, we aimed to verify the usefulness of BDNF methylation status as a predictor of treatment outcome. Material and Methods Our study included 30 female inpatients diagnosed with depression who underwent antidepressant treatment. Before starting treatment and after a minimum of 6 weeks, the level of methylation of the BDNF gene exon IV promoter was examined. Results. No statistically significant difference in the level of BDNF gene methylation before or after treatment was observed, and the usefulness of BDNF gene methylation as a prognostic factor for treatment response was not proven. Conclusions Further studies on a larger group of patients are necessary to verify whether the dynamics of methylation changes in the BDNF gene mirrors the results obtained in adults. Studies on this subject are essential to increase the effectiveness of depression treatment in adolescent patients.