Advanced inoperable/metastatic neuroendocrine tumors (NETs) pose a therapeutic challenge with limited treatment options. Peptide receptor radionuclide therapy (PRRT), being specific in targeting the somatostatin receptors, is a promising and viable option in this setting. In this study, we intended to evaluate the role of PRRT as the first-line systemic therapy in advanced inoperable/metastatic NETs. Data of consecutive patients of advanced inoperable/metastatic NETs treated with first-line Lu-DOTATATE at our center, from September 2012 to August 2019, were collected and analyzed. Forty-five patients (median age, 50 years; range, 14-72 years) with treatment-naive advanced NETs received a median cumulative dose of 27 GBq (range, 13.3-41.3 GBq; over 2-7 cycles) Lu-DOTATATE and 1250 mg/m capecitabine from days 0 to 14 of each PRRT cycle. Three patients were lost to follow-up, 2 had nonmeasurable lesions on CT, and hence, radiological response using Response Evaluation Criteria in Solid Tumors version 1.1 could be assessed in 40 patients. Twelve of 40 patients (30%) showed a partial response, whereas stable disease was observed in 22 of 40 patients (55%). Disease progression was limited to 6 of 40 patients (15%). Treatment-related adverse effects were minimal with grade 3/4 anemia, leukopenia, neutropenia, and hepatotoxicity observed in 2%, 2%, 4%, and 4% of the patients, respectively. Median progression-free survival was 48 months (95% confidence interval, 34.7-61.3 months). Our results indicate the efficacy and safety of first-line PRRT in advanced NETs. Future randomized trials, comparing PRRT and somatostatin analogs in treatment-naive patients, are required to identify the definite sequence of treatment options for these patients.