This paper reports a study on the performance of a multistage constructed wetland (CW) system adopted for winery wastewater and on the analysis of its suitability for irrigation reuse. The CW system treats about 3 m3·day−1 of wastewater produced by a small winery located in Sicily (insular Italy). Wastewater samples were collected at the CW inlet and outlet for physical–chemical and microbiological quality characterization. CW efficiency was evaluated on the basis of water quality improvement and of the achievement of Italian and EU irrigation reuse regulation limits. The CW system showed Chemical Oxygen Demand (COD) and Total Suspended Solids (TSS) mean removal rates of about 81% and 69%, and a maximum removal of about 99% (for both COD and TSS) occurred during grape harvest phase. The CW removal efficiencies for nutrients were 56% for TN and 38% for PO4-P, considering their low average concentrations at CW inlet. The CW system evidenced an effluent average quality compatible with the limits imposed by the Italian regulation and EU proposal regulation on the minimum requirement for water reuse. The CW vegetated area showed regular growth and vegetative development; phytotoxicity phenomena were not detected. The results of the study suggest the important role of CW systems in the treatment of winery wastewater and for their subsequent reuse in agriculture.