OBJECTIVE The aim of this study was to assess the efficacy and safety of cyproheptadine (CY) use in infants and young children with poor growth treated at our multidisciplinary pediatric feeding program, and to describe changes in their weight and feeding behaviors. METHODS A retrospective chart review of children treated with CY from January 2007 to July 2011 was performed. Demographic data, medical diagnosis, adverse effects of the drug, and changes in mealtime behaviors were extracted from the patients' medical records. For each patient who received the CY, weight-for-age z scores (WtZ) were calculated before and during treatment. Repeated-measures mixed model was used to analyze the pattern of change in WtZ over time and between groups. Differences in mean WtZ were tested between patients regularly receiving CY and a naturally conceived comparison group. RESULTS Of the 127 patients in treatment owing to poor weight gain who received the CY, 82 took the medication regularly as prescribed in combination with our interventional program. For these patients, the majority of the parents (96%) reported a positive change in mealtime and feeding behaviors. A significant improvement in mean WtZ was observed after starting CY when compared with the WtZ before treatment for those patients regularly receiving the medication. This effect was independent of patients' age and/or presence of an underline medical problem. No significant differences in mean WtZ were observed over time within the comparison group. CONCLUSIONS In our experience, the use of CY in combination with a specialized multidisciplinary interventional program is a safe and effective therapy in infants and young children with low appetite and poor growth.