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Summary: Background: During the SARS-CoV-2 pandemic, dominant viral variants were repeatedly replaced by new variants with altered properties, frequently changing the dynamics of the infection event, as well as the effectiveness of vaccines and therapeutics. SARS-CoV-2 variant monitoring by whole genome sequencing was established at the University Medical Center Mainz, Germany to support patient management during the pandemic. Methods: SARS-CoV-2 RNA samples from the University Medical Center were analysed weekly with whole genome sequencing. The genome sequences obtained were aligned with sequences from public databases to perform variant assignment. For classification purposes, phylogenetic trees were constructed to map the variant distribution in the clinical settings and the current outbreak events at that time. We describe the surveillance procedures using an example from a geriatric ward. Results: For monitoring, a time series was created covering two years of the pandemic. The changes from the Alpha to the Delta and the Omicron variants of SARS-CoV-2 could thus be precisely observed. The increasingly rapid switch of Omicron subvariants in the recent past could be tracked. The elucidation of phylogenetic relationships between circulating strains allowed conclusions about transmission pathways. Using an example from a geriatric ward, we demonstrated how variant monitoring by whole genome sequencing supported the infection prevention and control procedures on a ward and contribute to the control of outbreaks. Conclusions: This example of SARS-CoV-2 demonstrates the effectiveness of targeted, local monitoring by molecular variant analysis. The program proved to be instrumental in controlling an outbreak on a geriatric ward.