The potential benefits of applying microbial electrolysis cell (MEC) technology to wastewater treatment are clear and profound. Previous pilot studies have demonstrated a ‘proof of concept' with domestic waste at ambient temperatures, but have not yet treated waste to required discharge standards, and have not reached energy neutrality. In addition, these reactors have been many orders of magnitude smaller than would be needed for full scale wastewater treatment plants. Scale-up affects many of the parameters that underpin performance; understanding its impact will be vital to further progress. Modifying a previously tested cassette-style design, we reduced the internal resistance, and increased the module size by a factor of 16, constructing an MEC with six 1 m2 anodes. This created an anodic surface area to volume ratio of 34 m2 m−3. The system was operated at a hydraulic retention time of 5 hours on settled domestic wastewater for 217 days, producing more current than a scaled-down reactor, which was run in parallel. The large MEC produced 0.8 L of 93% pure H2 d−1 at ambient winter temperatures (11.4 ± 2.5 °C). Chemical oxygen demand (COD) removal averaged 63.5% with an average effluent quality of 124.7 mgCOD L−1, achieving the European Urban Wastewater Treatment Directive (1991) consent.