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(1) Background: Earwax might provide the long-term concentration of substances that are altered in chronic diseases. Standardised earwax extraction has to be exclusively performed by clinicians. We investigated the safety, reliability, and tolerance of a novel self-sampling earwax device in comparison with a clinical method; (2) Methods: We compared the reliability between both methods in a longitudinal study. We first cleaned both ears at baseline in 37 controls. Secondly, we obtained a sample a month after by extracting earwax from the right ear with a novel self-sampling device, and from the left ear by using the clinical method. Reliability of both methods was measured by coefficients of variation; (3) Results: The weight of the baseline samples was not significantly different between ear sides. The reliability of the two methods was not significantly different. The self-extraction method removed eight times more earwax than the clinical method. The new method proved to be well tolerated; (4) Conclusions: The novel device was as reliable as the clinical method in sampling earwax. In view of its practicality, safety, tolerability and efficiency, the new method may have clinical applications at a reduced cost.