This prospective randomized, double-blind factorial study aimed to compare the efficacy of three different intracanal medicaments with the placebo in controlling the postoperative pain after complete root canal preparation. The study was performed on 64 mandibular molars of 64 patients with diagnosis of pulp necrosis and acute apical periodontitis. After chemomechanical procedures using the stepback technique and 1% sodium hypochlorite, the teeth were randomized into four treatment groups (n=16). In group I, canals were filled with calcium hydroxide paste mixed with 2% chlorhexidine gel, group II received 2% chlorhexidine gel, group III was treated with calcium hydroxide paste, and group IV received no dressing (control). Before dismissal, preoperative pain experience was recorded using a visual analog pain scale. Patients were then instructed to quantify the degree of pain experienced 4h after treatment and daily for a further 24, 48, 72 and 96h. Two-way repeated measures ANOVA test and post hoc Tukey's HSD test revealed that at each time interval groups I and II were significantly more effective in reducing the postoperative pain values than groups III and IV (p<0.05). Dunnett's test showed that groups I and II differed significantly from control whereas difference between group III and control was not significant (p>0.05). Patients with pulp necrosis and acute apical periodontitis that had been dressed with chlorhexidine alone and calcium hydroxide plus chlorhexidine gave rise to less pain than that experienced by patients who had a calcium hydroxide dressing alone or no dressing at all.