Objective <p>¹⁷⁷Lu is an approved radionuclide for targeted radionuclide therapy (TRT), first established with ¹⁷⁷Lu-DOTATATE for neuroendocrine tumors, and subsequently with PSMA-targeted therapy. The widespread adoption of these therapies is expected to substantially increase radioactive waste generation. The long-lived isomer ¹⁷⁷ᵐLu, present as an impurity in ¹⁷⁷Lu preparations, may significantly affect the long-term radioactivity of urine waste. We aimed to quantify and compare the radioactivity of urine waste from real-world patients undergoing ¹⁷⁷Lu-TRT, with and without ¹⁷⁷ᵐLu impurities, to inform waste management strategies.</p> Methods <p>Radioactivity was measured in two components: vials and patient urine waste. Six vials produced by the direct production process (containing ¹⁷⁷ᵐLu impurities) and six by the no-carrier-added (n.c.a.) process (without ¹⁷⁷ᵐLu impurities) were measured using a dose calibrator. Urine waste from real-world patients treated with ¹⁷⁷Lu-DOTATATE (7.4 GBq per infusion, four infusions at 8-week intervals) was collected from a room under special safety measures for radionuclide therapy using a portable toilet system (Wrappon^®), stored under refrigerated conditions, and measured using a NaI scintillator at 1&#xa0;m. Measurements were performed at multiple time points up to 120 days post-treatment. A log-linear mixed-effects model was used for statistical analysis (R version 4.5.2).</p> Results <p>Vials and urine waste from the direct production route retained measurable radioactivity beyond 120 days. In contrast, those from the non-carrier-added route reached background levels by day 73.5 and day 77.0, respectively (both <i>p</i> &lt; 0.05).</p> Conclusion <p>No-carrier-added ¹⁷⁷Lu production, which eliminates ¹⁷⁷ᵐLu impurities, significantly reduces the long-term radioactive burden of urine waste and supports the safe expansion of targeted radionuclide therapy.</p>