The sewage epidemiology approach was applied to a one-year sampling campaign in the largest wastewater treatment plant (WWTP) in Belgium. The consumption of cocaine (COC), amphetamine (AMP), methylenedioxymethamphetamine (MDMA), methamphetamine (METH), methadone (MTD) and heroin (HER) was evaluated based on measured concentrations of the parent compound and/or metabolites in daily 24-hour composite influent wastewater samples. The inevitable back-calculations used in the sewage epidemiology approach were adapted to newly available information regarding the stability of the compounds in wastewater and the excretion pattern of illicit drugs. For COC, three different back-calculation approaches were evaluated. In addition, for the first time, efforts were made to calculate the number of inhabitants living in the catchment area of the WWTP in a real-time and dynamic way, based on concentrations of nitrogen, phosphorus and oxygen in the wastewater samples. Clear variations in the amount of inhabitants in the catchment area of the WWTP were observed. For COC, AMP and MDMA a significant higher weekend use was observed while for HER and MTD no significant daily variations could be found. METH consumption was negligible. Generally, the sewage epidemiology calculations were in agreement with official statistics. This manuscript shows that sewage epidemiology provides consistent and logical results and that it is a promising tool that can be used in addition to classical studies to estimate illicit drug use in populations. Therefore, efforts should be made to further optimize this approach in the future.