A 32-month monitoring program is presented in a vertical flow constructed wetland facility, located in North Greece. The monitoring campaigns were organized every 15 days. Water quality samples were collected at the inlet, at four intermediate points (i.e., at the end of each treatment stage) and at the outlet of the system. Temperature, electrical conductivity, pH and dissolved oxygen (DO) were measured in-situ with the use of appropriate instruments at the same points of water sample collection. Water samples were analyzed for biochemical oxygen demand (BOD), chemical oxygen demand (COD), total Kjeldahl nitrogen (TKN), ammonia, nitrate, nitrite, total phosphorus (TP), ortho-phosphate (OP), total suspended solids (TSS) and total coliforms (TC). Mean removal efficiencies for the monitoring period were: 90.8% for BOD, 89.0% for COD, 83.9% for TKN, 83.8% for ammonia, 38.8% for TP, 17.4% for OP, 90.4% for TSS and 99.9% for TC, indicating, for most pollutant, excellent performance of this constructed wetland (CW) system under Mediterranean climate conditions. Results showed that organic matter, TSS, TKN, ammonia, TP, OP and TC removal is not significantly affected by temperature. The collected removal data were used to produce appropriate parameter values for first-order k-C* models and develop simple models based on stepwise multiple linear regression (SMLR) analysis, in an effort to predict CW performance. These models were verified using data from another facility located in the same region. The results showed that the predictions correlate well with measured values, leading to the conclusion that the first-order models and the developed SMLR models are useful tools in the design of vertical flow (VF) CWs.