Objective:The objective of this study is to compare the antimicrobial efficacy of triple antibiotic paste (TAP) and a proton pump inhibitor (PPI) (omeprazole) in combination with calcium hydroxide (CH) against Enterococcus faecalis and Candida albicans.Materials and Methods:E. faecalis and C. albicans were subcultured and inoculated at 37° overnight and were treated with different dilutions of TAP, 25 μg/ml (Group 1), CH (Group 2, control), CH 16 mg/ml + omeprazole 2 mg/ml (Group 3a) (CH 16 mg/ml + omeprazole 4 mg)/ml (Group 3b) for 24, 48, and 72 h in sterile uncoated 96-well microtiter plates. Minimum concentration at which the medicaments produced least optical density was determined using ELISA reader (ELx 808 BioTek Inc., USA) device set at optical density of 630 nm. Results were analyzed statistically by one-way analysis of variance followed by Tukey's multiple comparison tests. The significance level was set at 0.05.Results:Mean concentration (irrespective of time) for TAP at which mean minimum optical density was recorded at 1.25 μg/ml (1:20 dilution) and 25 μg/ml (0 dilution) against E. faecalis and C. albicans, respectively. Least optical density for CH plus PPI group was obtained 1.6 μg/ml (1:10 dilution) and 16 μg/ml (0 dilution) for E. faecalis and C. albicans, respectively. However, CH alone showed a weaker antimicrobial action against either of the strains even at full concentration.Conclusions:PPI enhanced the antibacterial efficacy of CH against E. faecalis and C. albicans. However, TAP showed the best antibacterial property followed by CH plus PPIs against both the selected strains.