Background and Objectives: Fracture of rotary files in the root canal system is a relatively common incident that obstructs access to the apical region and negatively affects treatment outcome. This study aimed to compare the antimicrobial efficacy of 2% chlorhexidine (CHX) and Cupral paste along with electrophoresis in the apical region of root canals obstructed with a fractured instrument. Materials and Methods: In this ex-vivo experimental study, the root canals of 72 extracted single-rooted single-canal human teeth were instrumented, sterilized, and inoculated with Enterococcus faecalis (E. faecalis). A rotary file was intentionally fractured at 3 mm from the apex. The teeth were randomly divided into 6 groups of positive control, electrophoresis with 2% CHX, electrophoresis with Cupral paste, electrophoresis alone, irrigation with 2% CHX alone, and application of Cupral paste alone. The apical 3 mm of the root canals was then cut, and the number of colony-forming units (CFUs) in this region was counted. Data were analyzed by one- way ANOVA and Tukey’s test. Results: All interventions decreased the bacterial count in the apical region. The difference in the bacterial count was significant among the 6 groups (P=0.00). Electrophoresis with Cupral paste showed superior antimicrobial efficacy than other groups, but its efficacy was not significantly higher than that of electrophoresis with 2% CHX (P>0.05). Conclusion: Electrophoresis with 2% CHX and Cupral paste yielded comparably efficacy for reduction of E. faecalis count in the apical region of root canals obstructed by a fractured instrument.