•Two-phase olive-mill waste and cattle manure were anaerobically co-digested.•Start-up and stabilization stages were studied in semicontinuous stirred tank reactor.•Propionic accumulation was the key factor in the methanogenic phase inhibition.•Total period of 140 days was required to start-up and stabilization the process.•During the stable period the methane productivity was 0.34 LCH4/LRd at 40-d HRT. In this work, the start-up and stabilization stages of mesophilic anaerobic co-digestion of 2POMW and CM in a semi-continuously fed stirred tank reactor (SSTR) were analyzed. Volatile fatty acids (VFAs) were monitored and used as the main control parameter for the start-up and stabilization stages, as well as to evaluate the potential inhibition episodes. The results showed that accumulation of propionic acid was the key factor in the inhibition of the methanogenic phase, leading to process imbalance. To avoid the problems associated with inhibition by high VFA concentrations, several reinoculations were performed using a suitable inoculum adapted to VFA degradation. The start-up phase was carried out in batch conditions for 97 days, reaching a final concentration of propionic acid of 12.77 mg/L. From that moment, the reactor was fed in a semi-continuous mode with a hydraulic retention time (HRT) of 40 days. A total period of 140 days was required to achieve a stable performance of the reactor with a methane productivity of 0.34 LCH4/LRd.