BACKGROUND: Appropriate diagnostics to monitor disease trends and assess the effectiveness and impact of interventions are essential for guiding treatment strategies at different thresholds of schistosomiasis transmission and for certifying elimination. Field validation of these assays is urgently needed before they can be adopted to support policy decisions of the national programme for control and elimination of schistosomiasis in P.R. China. We compared the efficacy and utility of different immunoassays in guiding control strategies and monitoring the endemic status of S. japonicum infections towards elimination. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was conducted in seven villages with different transmission intensities settings to assess the performance and utility of three immunoassays, e.g., an indirect hemagglutination assay (IHA_JX), an enzyme linked immunosorbent assay (ELISA_SZ), and a dot immunogold filtration assay (DIGFA_SH). 6,248 individuals aged 6-65 years old who gave consent and supplied their stool and blood samples were included for data analysis. Results showed that ELISA_SZ performed significantly higher sensitivity (95.45%, 95%CI: 92.94-97.97%) than IHA_JX (87.59%, 95%CI: 83.51-91.49%) and DIGFA_SH (79.55%, 95%CI: 74.68-84.41%), especially in subgroups with very low infection intensity. The specificity of ELISA_SZ, IHA_JX, DIGFA_SH in 6-9 year olds with occasional exposure was nearly 90%. DIGFA_SH performed the highest screening efficacy for patients among three assays with overall positive predicative value of 13.07% (95%CI: 11.42-14.72%). We found a positive correlation of antibody positive rate of IHA_JX with results of stool examination in age strata (r = 0.70, P<0.001). Seropositivity of IHA_JX in children aged 6-9 years old showed an excellent correlation with prevalence of schistosome infection in the seven communities (r = 0.77, P<0.05). CONCLUSIONS/SIGNIFICANCE: Studies suggest that ELISA_SZ could be used to guide selective chemotherapy in moderate or low endemic regions. IHA_JX could be used to as a surveillance tool and for certifying elimination of schistosomiasis through monitoring children as a sentinel population.