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BACKGROUND AND AIMS Vaccination against COVID-19 is a promising strategy to reduce the risk for severe COVID-19. Patients on maintenance haemodialysis have a less robust immunoresponse than the general population. Triple vaccination might improve immunogenicity, and might benefit patients having a poor initial response. The aim of the current study was to evaluate the humoral response to heterologous (a combination of different vaccine types) versus homologous (three identical vaccines) triple vaccination against COVID-19. METHOD We analyzed serological response to homologous (3 times mRNA-based vaccine) versus heterologous (adenoviral vectored plus mRNA vaccines) triple regimens in samples from patients on maintenance dialysis (NCT04378686). We measured IgG anti–S (spike) SARS-CoV-2 antibody levels using the IgG II Quant assay (Abbott). Samples were collected between 6 and 12 weeks after both the second and the third vaccine dose. RESULTS A total of 302 patients received three vaccine doses. 94 patients received a heterologous regimen of the adenoviral vectored AZD1222 (2 doses) and the mRNA-based BNT162b2 (1 dose). The remaining 208 patients received a triple mRNA vaccine regimen of either BNT162b2 (n = 149) or mRNA-1273 (n = 59). Triple vaccine regimens resulted in significant elevation of anti-S titers, as compared with the conventional prime-boost (double) vaccination. A substantially and significantly larger fraction of patients reached the threshold for neutralizing antibodies after triple vaccination, as compared with after double vaccination. The yield of a third dose of mRNA-1273 is less than the yield of a third dose of BNT162b2. This, however, mainly reflects the initial significant better response to mRNA-1273. In multivariate analysis, a past episode of COVID-19 was a strong modulator of the response after double vaccination, and after triple vaccination. CONCLUSION Both heterologous and homologous triple vaccine regimens significantly augment the humoral response against SARS-CoV-2. The higher the ininitial response to the double prime-boost regimen, the lower the yield of a third vaccine dose. It seems prudent to prioritize vaccination of dialysis patients using mRNA-based vaccines when available.