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Aim and Background: The Difficulties in Emotion Regulation Scale (DERS) is a multi dimensional tool used in studies related to emotion regulation. The purpose of the present study was to compare the confirmatory factor analysis (CFA) approach and exploratory structural equation modeling (ESEM) in terms of evaluation of factor structure of the DERS. Methods and Materials: This was a descriptive-correlational study based on data obtained from 250 students of the University of Tabriz, Iran. The participants were selected through cluster sampling. To achieve the research objectives, the Persian version of the DERS was used. In this study, the CFA and ESEM approaches were applied using the Mplus software. Moreover, the comparison of CFA and ESEM methods was conducted through ΔCFI index. Findings: The results showed that contrary to the CFA method, the ESEM technique is a suitable method to assess the factor structure of DERS and offers a clearer view of its latent structure. The 25-itemstructure of the scale with 4 factors and no reverse-scored items showed the best fit. For this model, EMSEA, CFI, and TLI of equal to 0.064, 0.964, and 0.951, respectively, were obtained. Conclusions: The appropriate factor structure of the 25-item scale illustrates that reverse-scored items seem to be problematic in DERS application. Due to the removal of reverse-scored items in the present study, it is suggested that these items be replaced with direct-scored items and the fit of factor structure be evaluated in future researches.