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The intensive use of pesticides has raised environmental concerns due to their persistence and slow degradation, posing ecotoxicological risks. Despite regulatory measures, pesticide application remains high, leading to soil and water contamination. To effectively monitor and mitigate these impacts, selecting an appropriate and efficient extraction method for detecting pesticides in soil is critical. This study evaluated the effectiveness of two extraction methods in soil—QuEChERS and QuEChERSER—and assessed the persistence of three commonly used pesticides. A test was conducted using 13 pesticide standards, representing a wide variety of functional groups, to compare the two extraction methods. For the persistence study, a microcosm experiment was performed with three selected pesticides: pendimethalin, oxyfluorfen, and trifloxystrobin. These were chosen due to their agricultural relevance, potential human toxicity, and persistence in various environmental compartments. The impact of two organic amendments on their dissipation was also evaluated. The microcosms were incubated in dark chambers at room temperature for 21 days, and pesticide concentrations were analyzed using ultra-high-performance liquid chromatography–tandem mass spectrometry. Both methods were effective, though performance varied depending on the compound. QuEChERSER proved to be more efficient, requiring less time and fewer resources than the traditional QuEChERS method. Among the three pesticides tested, the herbicide oxyfluorfen was the most persistent, while the fungicide trifloxystrobin showed the least persistence. The application of organic amendments enhanced the dissipation of all three pesticides. These findings highlight the importance of selecting appropriate extraction techniques and adopting sustainable agricultural practices to mitigate pesticide residues in the environment. Full article