Fluoroquinolone antibiotics such as ciprofloxacin can be found in soils receiving exogenous organic matter (EOM). Their long-term behavior in EOM-amended soils and their level of biodegradability are not well understood partly due to a lack of methods to estimate their environmental availability. We performed different aqueous extractions to quantify the available fraction of C-ciprofloxacin in soils amended with a compost of sewage sludge and green wastes or a farmyard manure contaminated at relevant environmental concentrations. After minimizing C-ciprofloxacin losses by adsorption on laboratory vessel tubes, three out of eleven different aqueous solutions were selected, i.e., Borax, NaEDTA and 2-hydroxypropyl-β-cyclodextrin. During 28 d of incubation, the non-extractable fractions were very high in all samples, i.e., 57-67% of the initial C-activity, and the availability of the antibiotic was very low, explaining its low biodegradation. A maximum of 6.3% of the initial C-activity was extracted from soil/compost mixtures with the NaEDTA solution, and 7.2% from soil/manure mixtures with the Borax solution. The available fraction level was stable over the incubation in soil/compost mixtures but slightly varied in soil/manure mixtures following the organic matter decomposition. The choice of different soft extractants highlighted different sorption mechanisms controlling the environmental availability of ciprofloxacin, where the pH and the quality of the applied EOM appeared to be determinant.