Isotropic conductive adhesives (ICA) are gaining more and more application interests in electronic manufacturing, however, their failure mechanism is not been fully understood. In this paper we present reliability investigations on an encapsulated ICA flip chip interconnection. Experimental work included product lifetime measurement, cross section observation, and whole module warpage scanning. Results revealed that the chip-size effect on the ICA lifetime was obvious. A theoretical analysis was conducted with Finite Element Method (FEM) simulation. Viscoelastic models for adhesives and underfill materials were employed, and the comparison with an elastic model was made. Calculated equivalent stresses and shear stress fitted well with the experimental lifetime measurement, thus a lifetime relationship similar to the Coffin-Manson formula was established to predict the thermal fatigue life of an encapsulated ICA flip chip. Furthermore, the influences of underfill properties on the ICA reliability were discussed.