The influence of the total solid content on the performance of high-solids waste digestion has been investigated on a 50 L reactor. The feedstock was residual municipal solid waste. The reactor has been operated in semi-continuous mode during 3 periods at various total solid content in the inlet (22%, 26% and 30%). Steady-state results showed that the biogas and methane production was slightly lower at 30% TS in the inlet, with an increase of the volatile fatty acid concentration. Nevertheless, solid segregation occurred more likely at low inlet TS (22%). Referring to the volumetric biological activity, it appeared that the optimal TS in the reactor is closed to 20–22%. In our case, this would correspond to an inlet TS concentration of 26–28%. At such TS content, the segregation effect would be limited and the biological activity is kept at a high level.