The necessity and importance of fatigue failure to variable load has been appreciated as the structural design technique develops and use of high tensile steel is increasing. This is much more appreciated for a large ship such as VLCC. The rigorous fatigue analysis and safety assessment should be, hence, carried out at the design stage to avoid the possibility of fatigue failure and to achieve the design result having a sufficient structural safety to fatigue strength. This paper deals with an efficient spectral fatigue analysis of ship structures by introducing the concept of stress influence coefficient. In the process included are probabilistic loading analysis, evaluation of long-term distribution of stress range and estimation of fatigue life applying the spectral fatigue analysis. An integrated computer program has been developed in which reliability analysis to fatigue strength is also included and has been applied to D/H VLCC.