ANTIMICROBIAL EFFICACY OF 2-HYDROXYISOCAPROIC ACID (HICA) TOWARDS ENTEROCOCCUS FAECALIS AS ALTERNATIVE ENDODONTIC INTRACANAL MEDICAMENT Introduction: Antibiotics are used as intracanal medicaments in endodontic therapy. However, increasing antimicrobial resistance has led to research on alternative medications. 2-hydroxyisocaproic acid (HICA) is a derivative of leucine, a normal component of human plasma that shows potential as an intracanal medicament. Objective: To determine the antimicrobial efficacy of HICA against Enterococcus faecalis (E. faecalis). Methods: The antimicrobial activity was screened by measuring the Zone of Inhibition (ZOI) using the disk diffusion method, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The positive control was a Triple Antibiotic Paste (TAP) containing minocycline, metronidazole, and ciprofloxacin. Sixty-six teeth were prepared, and the canals were filled with E. faecalis suspension before incubation for 21 days. Later, HICA at a concentration of 16 mg/mL, TAP at 1 mg/mL, and saline (negative control) were introduced and further incubated for seven days under anaerobic conditions at 37°C. Viable bacterial counts in the canals were used as indicators of bacterial growth. Results: At 256 mg/mL concentration, HICA exhibited a ZOI of 15.72 ± 1.60 mm, and MIC and MBC were 8 mg/mL and 16 mg/mL, respectively. TAP, at a concentration of 4 mg/mL, exhibited a ZOI of 30.74 ± 0.71 mm, and its MIC was equal to MBC at 0.25 mg/mL. The viable bacterial counts extracted from the canal were 4.33 ± 0.23log10 for saline, 4.03 ± 0.21log10 for HICA and 3.97 ± 0.34log10 for TAP. Compared with saline, both TAP and HICA exhibited a significant difference in bacterial counts (p < 0.01). Interestingly, the efficacies of TAP and HICA were similar, with p-values of 0.79. Discussion: The ZOI indicated that HICA exhibited an antimicrobial effect. E. faecalis growth was repressed at 8 mg/mL, and cell death was observed at 16 mg/mL. At 16 mg/mL, HICA showed antimicrobial efficacy comparable to 1 mg/mL of TAP. Conclusion: HICA shows potential as an alternative intracanal medicament to eradicate E. faecalis in endodontic treatment.