A common problem in aircraft maintenance is the development of fatigue cracks at fastener holes due to stress concentration. High-frequency guided ultrasonic waves allow for the structural health monitoring of critical areas of a structure and can be measured with high accuracy using a noncontact laser interferometer. The use of a specific type of high-frequency guided ultrasonic wave that has good sensitivity for the detection of small defects, excited using a standard Rayleigh wedge transducer and propagating along the structure, has been investigated. Fatigue crack growth at the side of a fastener hole in a tensile, aluminum specimen was induced by cyclic loading of the structure. The crack length was monitored optically and showed good correlation with fracture mechanics calculations of the expected growth rate. The changes in the guided wave signal due to the fatigue damage were monitored using a noncontact laser interferometer and quantified. The measurements show a good sensitivity for the early detection of fatigue damage and for the monitoring of fatigue crack growth at a fastener hole. The propagation and scattering of the high-frequency guided ultrasonic wave has been simulated numerically using a three-dimensional finite difference code. Good agreement was found between the measured and predicted changes of the ultrasonic signal for the increasing fatigue crack area, allowing in principle for the approximate sizing of the defect.