The fatigue of structural details of ships is of great importance in the maritime industry as they can lead to cracks which can jeopardize structural integrity. The hopper knuckle is among the most vulnerable areas in a ship with respect to fatigue damage. Analysis of the hopper knuckle has become mandatory for tankers in the Class Ship Rules and in the International Association of Classification Societies Common Structural Rules. Along with the fatigue damage record of the vessels, the fatigue analysis of the hopper knuckles is essential to ensure that the vessels have sufficient fatigue strength. In the current work, fatigue calculations are performed of the upper and lower hopper knuckle connections within midship of the oil tanker using simplified fatigue calculations based on Det Norske Veritas (DNVGL) Classification Note No. 30.7. The fatigue analysis is based on 25 years of operation in worldwide wave environment. A cargo hold model (1/2 + 1 + 1/2) amidships and a local finite element model of the hopper knuckle are generated. The local model provides relevant hotspot stress for fatigue life calculations. The results from the hopper knuckle fatigue analysis show that the vessels may expect fatigue cracks at lower hopper knuckle before the vessel reaches its design life of 25 years. Based on the findings, it is recommended to fit soft brackets and close scallops at the lower hopper knuckle on selected common frames in all cargo holds.