Montelukast by inhibiting leukotriene receptors in the bladder can prevent the activation of mast cells. We investigated the effectiveness of Montelukast in reducing the symptoms of children with bladder pain syndrome (BPS). In this randomized clinical trial, children were allocated into groups of intervention (Montelukast and oxybutynin) and the control (oxybutynin). At the beginning and after 14 days, questions from mothers of children about their urinary condition were asked about the frequency of nocturnal enuresis, frequent urination, urinary incontinence, urinary urgency, and their pain severity. There was no significant difference between two groups in terms of frequency of nocturnal enuresis, frequent urination, urinary incontinence, and urinary urgency. Regarding the frequency of pain distribution, the frequency of pain-free people in the Montelukast group was higher than control group (84.4% vs 56.3%, P = .023). The results showed that adding Montelukast to oxybutynin has a significant decrease in pain in children with BPS.