Bubble Columns Are Widely Used in Chemical, Petrochemical, and Biochemical Industries for Various Processes Such as Alkylation, Oxidation, Chlorination, Wet Oxidation of Effluents, Etc. a New Hypothesis for Hydrodynamic Similarity that Can Be Subsequently Used for Scale-Up of Bubble Column Reactors Was Proposed. This Hypothesis Was Evaluated using Advanced Diagnostic Techniques. the Conditions of Similarity Where overall Gas Holdup and Radial Gas Holdup Profiles Were the Same, and Mismatch Where overall Gas Holdup Was the Same But Gas Holdup Radial Profiles Were Different, Were Identified. the Condition that Two Systems Must Operate in the Same Flow Regime to Be Hydrodynamically Similar Was Necessary But Not Sufficient. It Showed the Importance of Matching Gas Holdup Radial Profiles or Cross-Sectional Distributions in Two Systems, Even If Both the Systems Operate in the Same Flow Regime. Hence, the Traditionally Used Criterion for Hydrodynamic Similarity, based Only on Global Parameters, Can Be Fatal and Needs to Be Exercised with Prudence.