This study used the EGSB and IC reactors to treat the high-salt and high-concentration organic wastewater (high-salt fatty acid production wastewater) and compared their performances The experimental results showed that the optimal influent water quality thresholds for both bioreactors to treat this wastewater were a COD concentration of 18,000 mg/L and a sulfate ion concentration of about 8000 mg/L. The reactor operated well when C/S was greater than 2.8. In addition, the value of C/S should not be less than 1.5. This is due to that under this condition, the sulfate reduction process has a significant impact on the removal of COD, and MPB may be inhibited by sulfides. The organic load OLR should not be greater than 10 kgCOD/(m3·d). It was also found that the start-up time of the IC reactor with external circulation was slightly shorter, and the COD removal effect, gas production rate, and load tolerance were slightly better than those of the EGSB reactor, the best reflux ratio of the two reactors was 6:1. The appropriate rising flow rate was 0.4 m/h.