Objective: The aim of this study was the comparative evaluation of the effectiveness of orange oil, turpentine oil, and chloroform in dissolving gutta-percha and GuttaFlow discs. Materials and Method: Forty-five discs (10 mm in diameter and 2 mm in thickness) made from GuttaFlow and gutta-percha were prepared. After weighing the initial mass by using an analytical balance, specimens were randomly divided into 3 groups (n=15) according to solvent type. GuttaFlow and gutta-percha specimens were immersed in solvents for 10 min and then reweighed. The difference between the final and initial weights of specimens was considered the mass dissolved by solvents. Two-way ANOVA test with Bonferronni correction and Tukey test were used for the statistical analyses. Results: Chloroform dissolved significantly more gutta-percha (p=0.000) and GuttaFlow (p=0.000) than orange oil or turpentine. There was no statistically significant difference between the effectiveness of orange oil and turpentine oil in dissolving both gutta-percha (p=0.985) and GuttaFlow (p=0.713). Conventional gutta-percha discs dissolved in the solvents more than GuttaFlow discs did (p=0.000). Conclusion: Chloroform was more effective in dissolving conventional gutta-percha and GuttaFlow discs compared to orange oil and turpentine. Conventional gutta-percha dissolved more than GuttaFlow did in the tested solvents. Removal of GuttaFlow via chemical solvents could be more difficult than for conventional gutta-percha in retreatment cases.