Synthetic somatostatin analogs have been posed as a potential source of error in somatostatin receptor imaging through interference with tumor detection; however, experimental models and clinical studies have shown a complex mechanism of the effect of octreotide on tumors. The aim of this study was to assess whether 68Ga-DOTATATE uptake before treatment with long-acting somatostatin analogs differs from that after treatment. Methods: Thirty patients (15 men; age [mean ± SD], 64.6 ± 13.4 y) who had intermediately differentiated to well-differentiated neuroendocrine tumors and who underwent 68Ga-DOTATATE PET/CT scanning before and after receiving long-acting repeatable octreotide (Sandostatin LAR) were included in the study. The SUVmax and SUVmean of healthy target organs, residual primary tumor, and up to 5 lesions with the highest SUVmax in each organ were compared before and after octreotide treatment. Results: The mean time interval between the 2 68Ga-DOTATATE studies was 9.6 ± 7.2 mo, and the mean time gap between the last Sandostatin LAR injection and the second 68Ga-DOTATATE study was 25.1 ± 14.8 d. The pretreatment mean SUVmax and SUVmean were both significantly higher in the thyroid, liver, and spleen (P < 0.05) than the values measured after the administration of Sandostatin LAR. No significant differences were found among the uptake indices for residual primary tumor or any metastatic lesions in the liver, bone, lung, or lymph nodes before and after Sandostatin LAR administration (P > 0.05). Conclusion: Long-acting octreotide treatment diminished 68Ga-DOTATATE uptake in the liver, spleen, and thyroid but did not compromise tracer uptake in residual primary tumor and metastatic lesions. These findings have a direct impact on the interpretation of 68Ga-DOTATATE PET/CT scans.