The infantile colic is one of the most common complaints in the infancy; however, limited therapeutic approaches are described in the literature. Recently probiotics have been suggested as a potential strategy in the treatment of infantile colic. We conducted this study to investigate the efficacy of probiotics in relieving colic symptoms in Iranian infants. This double-blind clinical trial was performed among 70 infants aged 3 to 16 weeks with the presumed diagnosis of infantile colic according to Wessel criteria who were breastfed or formula fed. They were assigned at random to receive Pedilact® (Bifidobacterium infantis, Lactobacillus reuteri, and Lactobacillus rhamnosus) (N=33) or placebo (N=32). Demographic data were recorded in the questionnaires at the beginning of the study. The number of daily episodes of crying and fussiness, number of weekly crying days, and duration of crying were separately analyzed on 7, 21, and 30th  days of investigation. Baseline demographic data showed no statistically significant difference between intervention and placebo groups. Infants given Pedilact® showed a significant reduction in daily episodes of crying, duration of crying, and the weekly number of crying days at the end of the treatment period compared with those receiving placebo (P=0.000). On 21th day of the study, daily episodes of fuss and crying (P=0.032) and duration of crying reduced significantly in the intervention group in comparison to the placebo group (P=0.000). Administration of Pedilact® drop significantly improved colic symptoms by reducing crying and fussing times in breastfed or formula fed in Iranian infants with colic. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(7):405-411.