Purpose: Gold standard sentinel lymph node (SLN) mapping for breast cancer involves technetium-99m (99mTc) lymphoscintigraphy but has drawbacks. Indocyanine green (ICG) fluorescence allows real-time visualisation of lymphatics and nodes, but routine use is not established. This study compared efficacy and costs between ICG and 99mTc. Methodology: Prospective non-inferiority trial of early breast cancer patients undergoing SLN biopsy with ICG and 99mTc (2021-2024). Number of SLNs identified, including metastatic nodes, and rate of failed mapping, were compared. Surgeon reported ease of use surveyed based on Likert scale from “very easy” to “very difficult” (1-5). Non-inferiority margin of 6% utilised. Cost-minimisation analysis performed using micro-costing analysis. Registered on ANZCTR (ACTRN12621001033831). Results: 305 patients have been enrolled at the end of this 3 year trial. There were no adverse reactions. Mean number of SLNs identified with ICG and 99mTc was 2.06 (SD 1.99) and 2.07 (SD 2.02), respectively (p = 0.871). Metastatic SLNs were identified in 70 of 305 (22.95%) patients, with 83 metastatic SLNs in total, which represented 13.03% of all 637 SLNs removed. ICG identified 79 of 83 (95.2%) positive SLNs and 99mTc identified 82 of 83 (98.8%) (p = 0.256). Mean surgeon reported ease for using ICG and 99mTc was 1.67 (SD 0.98) and 1.5 (SD 0.59), respectively (p = 0.082). Technetium-99m cost an additional AU$1492.72 per case but ICG would require >35 cases before breaking even with initial outlay equipment costs. Conclusion: ICG fluorescence was equivalent to 99mTc lymphoscintigraphy in terms of number of SLNs identified, including metastatic nodes, rate of failed mapping and safety, and was less costly long-term.