Nilotinib, a second generation tyrosine kinase inhibitor, has remarkably improved outcomes in patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia by targeting BCR-ABL1 fusion protein. Despite the safety and efficacy of these agents, adverse side effects can occur due to unintended inhibition of off-target kinases. While the clinical ramifications of serosal inflammation - including pleural and pericardial effusions - have been a common occurrence in patients on older tyrosine kinase inhibitors (TKI), the effect of nilotinib causing pericardial effusion is rare. This case report highlights a rare occurrence of pericardial effusion while being treated with nilotinib for chronic myeloid leukemia.