Some of the key factors affecting the adaptation of anaerobic digestion processes to increasing levels of salinity were determined in batch tests using brown seaweed as a feedstock. It was found that cultures seeded with non-saline anaerobic inoculum required an adaptation period of up to two months to reach the same level of methane production rate as in those cultures seeded with saline-adapted inoculum. The Anaerobic Digestion Model No.1 (ADM1) was modified to include an extra inhibition function to account for the effect of salinity, and calibrated using a set of experimental data obtained from batch biochemical methane potential tests. After calibration, the model was able to accurately predict methane production rates. Thus, the results show that, in the absence of saline-adapted inoculum, non-saline inoculum can be used for the start-up of anaerobic digestion systems treating saline-rich feedstocks.