Renewable fuels, such as the alcohols, ammonia, and hydrogen, have a high autoignition resistance. Therefore, to enable these fuels in compression ignition, some modifications to existing engine architectures is required, including increasing compression ratio, adding insulation, and/or using hot internal residuals. The opposed-piston two-stroke (OP2S) engine architecture is unique in that, unlike conventional four-stroke engines, the OP2S can control the amount of trapped residuals over a wide range through its scavenging process. As such, the OP2S engine architecture is well suited to achieve compression ignition of high autoignition resistance fuels. In this work, compression ignition with wet ethanol 80 (80% ethanol, 20% water by mass) on a 3-cylinder OP2S engine is experimentally demonstrated. A load sweep is performed from idle to nearly full load of the engine, with comparisons made to diesel at each operating condition. These results indicate that on the OP2S architecture, wet ethanol 80 produces near-zero soot and reduces engine-out NOx emissions by a factor of 3-5. Due to the combustion chamber geometry, which is optimized for diesel combustion, most of the fuel was injected near top dead center for a diffusion-style heat release process. Therefore, there is 1-3 percentage point thermal efficiency penalty associated with wet ethanol 80’s longer diffusion heat release process, since the nozzle hole size of the injector was not increased, and from evaporation-driven heat removal near top dead center. However, further optimization of the injectors and combustion chamber geometry could mitigate or eliminate this efficiency penalty by enabling a larger fraction of the total fuel to be injected earlier in the compression stroke.