The Airbus A380 was initially expected to replace existing aircraft due to its remarkable fuel efficiency on long-haul routes when operating with a full passenger load. However, recent changes in the commercial aviation environment have resulted in a decrease in demand for four-engine aircraft. Rising fuel prices have pushed airlines to focus on more efficient operations, while manufacturers prioritize producing advanced twin-engine aircraft. The debate over the long-term economic viability of A380 operations remains ongoing. This study compares and evaluates the fuel efficiency of the Airbus A380 and the Airbus A350 using actual flight data. The analysis employs a fuel efficiency prediction model to compare scenarios based on identical payload and load factor. Results indicate that the A350 is approximately twice as fuel efficient as the A380 under the same payload and about 1.34 times more efficient under the same load factor. The A380’s economic viability is analyzed by considering the balance between revenue per available ton-kilometer (RASK) and cost per available ton-kilometer (CASK). If the A380’s RASK is significantly higher than 1.34 times the A350’s or exceeds its own CASK, it can sustain operations. Achieving a balance between RASK and CASK is essential for the economic sustainability of A380 operations.