The comparative process stability and efficiency of mesophilic anaerobic digestion (35 degrees C) has been evaluated for four different reactor configurations, which are: daily batch-fed single-stage continuously stirred tank reactor (CSTR) (MB), continuously fed single-stage CSTR (MC), daily batch-fed two-phase CSTR (MTP), and daily batch-fed non-mixed single-stage reactor (MNMR). The results are discussed for 2 periods, 1) start-up until steady state (HRT = 20 days, Days 0-200) and 2) OLR increase from 4% solids at steady state to reactor failure by increasing solids concentration in the feed and decreasing the HRT (Days 201-). During the start-up period, the MB showed the lowest stability with a pH drop whenever the solids concentration in the feed was increased. Conversely the MNMR reached steady state with 4% feed solids inthe shortest time with a relatively stable pH and low VFA. The superior performance of the MNMR confirms the importance of microbial consortia proximity especially for the removal of propionate. A cocktail of nutrients (Ca, Ni, Fe, and Co) was added daily into the reactors which showed high VFA except the MNMR which did not exhibit the elevated VFA. The results indicated that adding nutrients stimulated gas production and facilitated removal of almost all VFA except propionate confirming the importance of inorganic nutrients bioavailability. During the long-term operation with OLR increase until reactor failure (pH below 55), the results show that the MC reached the highest OLR while the MNMR failed first. Compared with the daily batch fed reactors, the constant pH of the MC seems to be the reason why the MC reached the highest OLR. Considering the best performance of the MNMR during the start-up period, the failure of the MNMR first is hypothesized to be due to the lack of trace nutrients at high OLR. Overall, two-phase digestion showed no benefit over single stage and all reactors demonstrated comparable VS removal percentage. Additional experiments in which the reactor configuration was changed from CSTR non-mixed reactor showed significant benefit with respect to gas production and lowered propionate threshold concentration. This once again manifests the importance of microbial consortia proximity with respect to the degradation of propionate.