Inflammation of the myocardium (myocarditis), pericardium (pericarditis), or both (myopericarditis) is a rare but potentially lethal side effect of mesalamine, a drug widely used in the treatment of inflammatory bowel disease (IBD). A 64-year-old female with a history of ulcerative colitis on mesalamine presented with dyspnea and chest pain. The patient was found to have mild to moderate pericardial effusion with signs of pericarditis. Further workup revealed positive rheumatoid factor, antineutrophil cytoplasmic autoantibody, cytoplasmic (c-ANCA), and antinuclear antibodies (ANA), raising suspicion for rheumatoid-associated pericarditis. She was discharged with a prednisone taper and an outpatient rheumatology follow-up. However, the patient presented again in three months with similar complaints and was found to have recurrent pericarditis. On this admission, mesalamine-induced pericarditis was considered in the differential diagnosis, and it was stopped on discharge. On a three-month follow-up, the patient showed complete resolution. Mesalamine-induced pericarditis is a rare side effect of this drug, and prompt recognition and appropriate intervention are important to prevent the progression of the inflammation and avoid adverse cardiovascular outcomes. The association of IBD with extra-intestinal cardiac manifestations can delay early diagnosis and treatment.