The use of waste-derived fertilizers, also known as bio-based fertilizers (BBFs), for the production of ready-to-eat vegetables can efficiently contribute to sustainability and circularity. However, studies on the efficiency and safety of these fertilizers are needed. Thus, this study aimed to examine and characterize the effects of combined application of BBFs on lettuce yield and quality and soil properties in a trial conducted under open field conditions. The eight experimental treatments included green-or food waste compost combined with either human urine, food waste digestate or synthetic fertilizer and compared to treatments with synthetic fertilizer alone or in combination with manure. The control treatment received no BBF or other type of fertilizer. The results showed statistically similar fresh lettuce yields after 48 days among the treatments, all of which were larger than the yield of the unfertilized control treatment. The highest fresh yield (73 t ha-1) was observed with the combination of manure and synthetic fertilizer. Yield in treatments that received green waste or food waste composts tended to decrease slightly, more likely due to nitrogen immobilization after the application of incompletely stabilized composts and the low initial mineral N. Nitrate contents in fresh lettuce leaves were below the EU limits (3000 mg kg-1) in all the treatments. Analysis of pathogens and trace elements present in aboveground lettuce showed no significant risk. The application of BBFs also appeared to maintain the soil pH compared to synthetic fertilizer treatments. The important nutrient and carbon contents of BBFs and their positive effect on lettuce yield associated with their non-harmful impact on lettuce quality suggest that BBFs can be used for vegetable production and to increase the soil carbon stocks and contribute to city sustainability.