Starting from the premise that vulnerability curves are an indispensable ingredient of earthquake loss assessment, this paper focuses on establishing the relative effect of strong-motion variability and random structural parameters on the ensuing vulnerability curves. Moreover, the effect of the selection of statistical models used to present simulation results is studied. A three story ordinary moment resisting reinforced concrete frame, previously shake-table tested, is used as a basis for the fragility analysis. The analytical environment and the structural model are verified through comparison with shaking-table test results. The selection of ground motion sets, definition of limit states, statistical manipulation of simulation results, and the effect of material variability are investigated. No approximations are used to reduce the sample size or minimize the analytical effort, in order that attention is focused on the parameters under investigation. Notwithstanding the limited scope of the study, the results presented indicate that the effect of randomness in material response parameters is far less significant than the effect of strong-motion characteristics. Therefore, the importance of scrupulous selection and scaling of strong-motion and use of appropriate limit states and statistical models is emphasized.