The motivation for this study is to contribute to the implementation of an innovative and thermally efficient distillation concept, which involves integrating a multi-tube type falling-film distillation column with a biphasic thermosyphon. This study concentrated on examining a startup operation with pilot-scale experiments at a feeding capacity of 250 kg h−1; while examining two possible thermal energy transfer arrangements from the steam chamber to the distillation tubes (isothermal and non-isothermal). The dynamic behavior of the startup operation was analyzed, revealing three distinct phases - discontinuous, semi-continuous, and continuous - each characterized by their respective time requirements and energy consumption. Using non-isothermal heating, the multi-tube falling-film distillation column required 11.2 kW for the startup operation, 17% less than isothermal heating. Operating under both heating configurations, the multi-tube falling-film distillation column achieved a 70 vol% ethanol concentration. Multi-tube falling-film distillation requires 51.0% less time and 72.1% less electrical energy during startup operation than traditional tray distillation. The knowledge obtained from this study can improve the efficiency of falling-film distillation columns, ensuring optimal industrial-level operation, and can contribute to the recognition of this recently developed technology in comparison to established conventional tray columns.