The Cellular Thermal Shift Assay (CETSA) enables the study of protein-ligand interactions in a cellular context. It provides valuable information on the binding affinity and specificity of both small and large molecule ligands in a relevant physiological context, hence forming a unique tool in drug discovery. Though high-throughput lab protocols exist for scaling up CETSA, subsequent data analysis and quality control remain laborious and limit experimental throughput. Here, we introduce a scalable and robust data analysis workflow which allows integration of CETSA into routine high throughput screening (HT-CETSA). This new workflow automates data analysis and incorporates quality control (QC), including outlier detection, sample and plate QC, and result triage. We describe the workflow and show its robustness against typical experimental artifacts, show scaling effects, and discuss the impact of data analysis automation by eliminating manual data processing steps.