To compare the efficacy of calcium hydroxide powder mixed with 0.2% chlorhexidine digluconate or mixed with normal saline as intracanal medicament in the treatment of apical periodontitis. Subjects were 55 in number aged 17 to 60 years. Two-visit conventional root canal treatment was performed on 70 teeth. The teeth were divided by randomization (balloting) into two groups: control group and experimental group, each with 35 teeth treated with calcium hydroxide mixed with normal saline or with 0.2% chlorhexidine digluconate as intracanal medicament respectively. All treated teeth were evaluated clinically and radiographically for signs and symptom of periapical infection at specified periods postoperatively. Overall efficacy of medicament was rated based on quality guidelines for endodontic treatment by the European Society of Endodontology 2006. A postoperative favorable outcome of 97.1% in the control group and 94.3% in the experimental group was observed at 6-month review. This difference was not statistically significant (p > 0.05). The use of normal saline or 0.2% chlorhexidine digluconate to mix calcium hydroxide used as intracanal medicament during endodontic treatment resulted in high postoperative favorable outcomes. Efficacy of 0.2% chlorhexidine digluconate as a vehicle for mixing calcium hydroxide as an intracanal medicament in the treatment of apical periodontitis is comparable to the efficacy of calcium hydroxide mixed with normal saline.