The ongoing miniaturization trend in the microelectronic industry enforces component sizes to approach the micron, or even the nano scale. At these scales, the underlying microstructural sizes and the geometrical dimensions are comparable. The increasing influence of microscopic entities on the overall mechanical properties makes conventional continuum material models more and more questionable. In this study, the thermomechanical reliability of lead-free BGA solder balls is investigated by microstructural modeling. Microstructural input is provided by orientation imaging microscopy (OIM), converted into a finite element framework. Blowholes in BGA solder balls are examined by optical microscopy and a statistical analysis on their size, position and frequency is conducted. Combining the microstructural data with the appropriate material models, three dimensional local models are created. The fatigue life of the package is determined through a critical solder ball. The thermomechanical reliability of the local models are predicted using cohesive zone based fatigue damage models. The simulation results are validated by statistical analyses provided by the industry.