Purpose Lutetium Lu-177 dotatate is the first peptide receptor radionuclide therapy approved by the US Food and Drug Administration. Well-designed studies in Europe have shown dramatic effectiveness in improving progression-free survival in patients with gastroenteropancreatic neuroendocrine tumors, which are progressive and generally metastatic. This therapy is a molecular targeted therapy linking a beta-emitting radioisotope to dotatate, which binds tightly to somatostatin receptors on neuroendocrine tumors cells. Various adverse effects of this therapy have been reported in the literature, including potential toxicity to renal, hepatic, and hematologic tissues and risk of second malignancy. Our study sought to explore acute adverse effects in this patient population. Methods and Materials We tracked adverse effects and patient experience in our first year of therapy experience with this new agent. Results In our first 12 patients who received Lutetium Lu-177 dotatate, tumor flare reactions occurred in 5 patients due to worsening symptoms of bone or soft tissue metastasis. This flare reaction can be mitigated with short course of corticosteroid therapy or other strategies. Conclusions Flare reaction is common in patients with progressive metastatic gastroenteropancreatic neuroendocrine tumors and can be managed successfully with several strategies.