Pruritus is a distressing symptom in burns rehabilitation and its treatment represents a challenge for the multidisciplinary burns team. We conducted a comparative study of two different therapeutic approaches in hospitalized burns patients using a combination of pharmacological agents. The observed symptomatic response to gabapentin as monotherapy as well as in combination therapy with two antihistamines was higher than chlorpheniramine alone and in combination with another two antihistamines (t = 3.70, df = 89, P < .001 for monotherapy and chi(2) = 12.2, df = 1, P = .001 for polytherapy). Patients with higher initial itch scores needed a combination of pharmacologic agents for effective symptomatic relief. A linear regression model showed that the likelihood of failure of monotherapy was marginally associated with decreasing patient age (P = .013) and increasing TBSA (P = .021, sum of square = 1.986, df = 2, P = .04). A combined approach using centrally and peripherally acting agents is most effective in the treatment of acute burns pruritus.