This study is directed toward an experimental investigation of formation damage in a large heterogeneous reservoir from the Middle East. A number of experiments using real reservoir core samples at reservoir conditions of pressure and temperature have been performed. Various drilling fluid contact times with the formation and overbalance pressures have been used during these experiments. The analysis of the experimental data shows that the results have been predominantly marked by the heterogeneous nature of this reservoir. The heterogeneity of the cores affects to a great extent how the damage due to drilling fluids occurs. The results show as expected that the damage permeability increases with the contact time. As a consequence, extended drilling causes additional formation damage and higher skin. Also, without contradicting the detrimental effect of the overbalance pressure on formation damage, the experimental data show an unexpected result: Higher permeability zones of the reservoir are affected much more significantly by the drilling fluids' damage than lower permeability zones. Similar results are obtained for invasion depth. The effect of the magnitude of the permeability on formation damage is so strong that it masks the effect of overbalance pressure on formation damage. A straight-forward conclusion is that stimulation jobs in such reservoirs should have as a primary objective to stimulate in priority the most permeable zones that have been damaged along the horizontal well instead of the low permeability zones since it pays more to regain a fraction of a very high permeability than the same or smaller fraction of a low permeability zone. Another conclusion of this study is that it is of paramount importance in formation damage to assess accurately the effect of the horizontal well effective length and its contribution to the productivity of the well compared to other parameters such as the damage permeability, the invasion depth, or the anisotropy ratio.