Purpose: Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor. Methods: Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving 90Y-DOTATOC, 177Lu-DOTATOC or their combination. Results: 90Y-DOTATOC plus 177Lu-DOTATOC treatment was associated with longer survival than 90Y-DOTATOC (66.1 vs. 47.5months; n = 1,358; p < 0.001) or 177Lu-DOTATOC alone (66.1 vs. 45.5months; n = 390; p < 0.001). 177Lu-DOTATOC was associated with longer survival than 90Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1-0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3-0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05-0.4; n = 113; p = 0.001). 90Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5% vs. 4.0%, p = 0.005) or 177Lu-DOTATOC (9.5% vs. 1.4%, p = 0.002). Renal toxicity was similar among the treatments. Conclusions: Using 90Y and 177Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors