Abstract: Environment and health quality of vegetable are closely related with food quality and human health. Most farmers use excessive chemical fertilizers to maximize yield. This practice, along with high irrigation and multiple cropping, results in soil degradation, nitrogen (N)/phosphorus (P) loss, and other severe environmental issues. A field experiment was carried out in a vegetable field of suburban Changsha City to determine the effects of reduced and optimized application of N fertilizer on soil nutrient balance and yield of lettuce. N was reduced by 20% under optimized fertilization strategies of slow-release urea (80%N+CRU), urease/nitrification inhibitor (80%N+QD) and soil conditioner (80%N+SC). The results showed that the three optimized strategies reduced soil NO₃^--N, Olsen-P content and nitrification rate. This reduced N/P loss into the environment and enhanced nitrogen use efficiency. It also increased lettuce biomass and farmers’ real income, with obvious economic and environmental benefits. The 80%N+CRU strategy significantly reduced soil NO₃^--N, Olsen-P contents and the loss of N and P into the environment. Compared with conventional fertilizer treatment (CF) and national standard (GB18406.1—2001) (P<0.05), however, it increased nitrate in the stem of lettuce at harvest. The 80%N+QD strategy had no significance effects on soil Olsen-P and nitrate in edible parts of lettuce. It, however, significantly reduced soil nitrification rate (P<0.05) and increased biomass yield by 21.7% for stem, 7.6% for leaf; and increased total revenue by 13.0%, farmers’ real income by 14.0%, and output/input ratio by 14.2%. The 80%N+QD strategy was therefore recommended as the optimal strategy. Although the effect of 80%N+SC treatment was not completely satisfactory, it improved the nutrient use efficiency. On accounts of comprehensive production effects, health safety and ecological benefits, it was suggested that the application of urease/nitrification inhibitors with reduced nitrogen fertilizer should be adopted in fertile vegetable soils.