There is much debate about whether the (mostly synthetic) pesticide active substances (AS) in conventional agriculture have different non-target effects than the natural AS in organic agriculture. We evaluated the official EU pesticide database to compare 256 AS that may only be used on conventional farmland with 134 AS that are permitted on organic farmland. As a benchmark, we used (i) the hazard classifications of the Globally Harmonized System (GHS), and (ii) the dietary and occupational health-based guidance values, which were established in the authorization procedure. Our comparison showed that 55% of the AS used only in conventional agriculture contained health or environmental hazard statements, but only 3% did of the AS authorized for organic agriculture. Warnings about possible harm to the unborn child, suspected carcinogenicity, or acute lethal effects were found in 16% of the AS used in conventional agriculture, but none were found in organic agriculture. Furthermore, the establishment of health-based guidance values for dietary and non-dietary exposures were relevant by the European authorities for 93% of conventional AS, but only for 7% of organic AS. We, therefore, encourage policies and strategies to reduce the use and risk of pesticides, and to strengthen organic farming in order to protect biodiversity and maintain food security.