Purpose <p>To assess risk factors for peptide receptor radionuclide therapy (PRRT)-related toxicity to the kidneys, liver, and bone marrow (BM).</p> Methods <p>This is a retrospective study of patients with advanced, well-differentiated neuroendocrine neoplasms treated with ¹⁷⁷Lu-DOTATATE. Serial blood tests for complete blood count, kidney function, and liver function tests were drawn before and 2–4&#xa0;weeks after each PRRT cycle. Toxicity was defined based on the Common Terminology Criteria for Adverse Events (CTCAE). Patients’ parameters were compared to assess the risk of PRRT-related toxicities; correlation analysis between baseline, post-cycle parameters, and their ratios was performed. Multivariable analysis was performed to identify independent predictors for PRRT toxicity.</p> Results <p>In 178 PRRT cycles in 47 patients (53.2% women, median age 65&#xa0;years), eight patients had hematological toxicity grade ≥ 2 and seven had hepatic toxicity. A positive correlation was found between baseline and post-treatment BM, kidney, and liver markers. Similarly, a positive correlation was found between the post-treatment-to-pre-treatment marker ratio in the first cycle and the full-treatment-to-baseline ratio. Women had a more pronounced decrease in blood WBC count (last/1st measurement ratio, 0.52 ± 0.17 vs. 0.72 ± 0.19, p &lt; 0.001, women vs. men, respectively), with a similar trend for hemoglobin (Hb) concentration (0.97 ± 0.08 vs. 1.01 ± 0.10, p = 0.090) during treatment. In the logistic regression, women’s risk for neutrophil impairment was 8.7 times higher than men’s (p = 0.034).</p> Conclusion <p>Baseline assessment reflects the patient’s reserves and their post-PRRT state. Further, women are more prone to BM-related toxicity from PRRT. These insights can help optimize treatment strategies and improve patient outcomes in this population.</p>