One of the complex processes of permeability impairment in porous media, especially in the near-wellbore region, is asphaltene-induced formation damage. During production, asphaltene particles precipitate out of the bulk fluid phase because of pressure drop, which might result in permeability reduction caused by both deposition of asphaltene nanoparticles on porous-medium surfaces and clogging of pore throats by larger asphaltene agglomerates. Experimental data will be used to identify the parameters of an impairment model being developed. As part of a larger effort to identify key mechanisms of asphaltene deposition in porous media and develop a model for asphaltene impairment by pressure depletion, this paper focuses on a systematic design and execution of an experimental study of asphaltene-related permeability damage caused by live-oil depressurization along the length of a flow system. An experiment was performed using a custom-designed 60-ft slimtube-coil assembly packed with silica sands to a permeability of 55 md. The customized design included a number of pressure gauges at regular intervals along the coil length, which enabled real-time measurement of the fluid-pressure profile across the full length of the slimtube coil. The test was performed on a well-characterized recombined live oil from the Gulf of Mexico (GOM) that is a known problematic asphaltenic oil. Under a constant differential pressure, the injection flow rate of the live oil through the slimtube coil decreased over time as the porous medium became impaired. During the impairment stage, samples of the produced oil were collected on a regular basis for asphaltene-content measurement. After more than 1 month, the impairment test was terminated; the live oil was purged from the slimtube coil with helium at a pressure above the asphaltene-onset pressure (AOP); and the entire system was gently depressurized to bring the coil to atmospheric conditions while preserving the asphaltene-damaged zones of the coil. The permeability and porosity of the porous medium changed because of asphaltene impairment that was triggered by pressure depletion. Results indicated that the coil permeability was impaired by approximately 32% because of pressure depletion below the AOP, with most of the damage occurring in the latter section of the tube, which operated entirely below the AOP. Post-analytical studies indicated lower asphaltene content of the produced-oil samples compared with the injecting fluid. The distribution of asphaltene deposits along the length of the coil was determined by cutting the slimtube coil into 2- to 3-ft-long sections and using solvent extraction to collect the asphaltenes in each section. The extraction results confirmed that the observed permeability impairment was indeed caused by asphaltene deposition in the middle and latter sections of the coil, where the pressure was less than the AOP. With the success of this experiment, the same detailed analysis can be extended to a series of experiments to determine the effects of different key parameters on pressure-induced asphaltene impairment, including flow rate, wettability, and permeability.