This retrospective chart review evaluates the outcomes of mesalamine treatment in infants with severe food protein-induced allergic proctocolitis (FPIAP) and persistent clinical symptoms despite the use of elemental formulas. Patients received mesalamine in a 40–60 mg/kg/d dose for an average of 100 days. This group showed significantly higher rates of improvement in the most common symptoms of FPIAP compared with the control group. In addition, the mesalamine group was less likely to need pharmacological treatment for gastroesophageal reflux disease and more likely to successfully transition to whole milk or soy milk after 1 year of age. In conclusion, using mesalamine can be a useful addition to the treatment of severe refractory cases of FPIAP.