Background: The aim of this clinical study was to evaluate and compare the clinical efficacy of subgingival ultrasonic mechanical instrumentation (UMI) irrigated with essential oils (EOs) and chlorhexidine (CHX) at the furcation involvements (FI). Methods: Forty-five patients (244 FI) who presented with Class II FI were recruited to the study. Patients were randomly assigned to CHX (UMI irrigated with 0.2% CHX), EO (UMI irrigated with EOs) or control (UMI irrigated with distilled water) groups. All treatments were performed in one session. For all groups, plaque index (PI), gingival index (GI), position of gingival margin (PGM), pocket depth (PD), bleeding on probing (BOP), clinical attachment level (CAL) and horizontal attachment level (HAL) scores were recorded at baseline and 1 and 3 months after therapy. Results: In all groups, there were significant reductions in PI, GI, PD and BOP, increase in PGM scores and gain in CAL and HAL scores, at 1 and 3 months compared to baseline. Except in BOP scores, there were no significance differences among the groups at any time point. At 1 and 3 months, there were significant reductions in the BOP scores of the EO group compared with the CHX and control groups. Conclusion: Within the limits of this study, the use of EOs as a cooling liquid of UMI may promote slight adjunctive effects at FI compared to CHX and water.