In this paper we focus on the thermo-mechanical reliability of flip-chip assemblies which are, in addition to periodic thermal loads, constrained by mechanical boundary conditions caused by the attachment of a heat-spreader. Whereas mechanically unconstrained flip-chip assemblies have been in the focus of reliability studies for a long time, the loading induced by additional mechanical constraints and hence the impact on solder bump reliability is still largely unknown. So a comprehensive study was carried out comprising FE-simulations for lifetime prediction and thermal cycling tests for experimental verification. For this purpose a tool for modular parametric FE-model generation was developed. The experiments do coincide with the simulative prediction with good accuracy, allowing for the first time a distinct statement about the reliability of flip-chip packages with attached heat-spreaders. As a result we have found that in general all additional constraints on the chip do reduce its lifetime. A distinct ranking has be obtained as a function of the specified variables. Eventually design guidelines are given.