Introduction Radioembolisation with ⁹⁰Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients’ dosimetric data were reviewed according to the linear–quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective. Materials and methods Twenty patients with metastatic lesions underwent radioembolisation. The ⁹⁰Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting α/β = 2.5 Gy (NTL), 10 Gy (tumours); T _1/2,eff = T _1/2,phys = 64.2 h; T _1/2,rep = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated. Results In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9–3.2) GBq, tumour dose was 130 (65–235) Gy, and tumour BED was 170 (75–360) Gy. Considering two cycles, ∼15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10–35) Gy; tumour BED increase was 10 (3–11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was ∼50 Gy (two cycles) and 65 Gy (three cycles). Conclusions From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested.

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