This paper presents a reliability analysis of steel I-beams with rectangular web openings, based on a combination of the common probabilistic reliability methods, such as RSM, FORM and SORM and using data obtained from experimental tests performed at the Istanbul Technical University. A procedure is proposed to obtain the optimum design load that can be applied to this type of structural members, by taking into account specified target values of reliability indices for ultimate and serviceability limit states. The goal of the paper is to present an algorithm to obtain more realistic and economical design of beams and to demonstrate that it can be applied efficiently to steel I-beams with web openings. Finally, a sensitivity analysis is performed allowing to ranking the random variables according to their importance in the reliability analysis.