It is generally understood that the cytology work process can be stressful and fatiguing affecting technicians’ performance and job satisfaction on a day-to-day basis and in the longer term. This study assessed the performance and user experience of cytotechnologists (CTs) reviewing liquid-based cytology samples using a new digital cytology platform Genius Digital Diagnostics System (Genius DxS) benchmarked against ThinPrep Integrated Imager (I2), to understand the impact of perceived stress, fatigue, and decision-making processes.