Due to the impact that pollution generates, especially due to the presence of pharmaceutical type traces in wastewater, it is necessary to develop and optimize biological treatment systems that are able to remove these pollutants and control the impacts that have been unleashed in natural environments. Therefore, this study evaluated the efficiency of anaerobic microorganisms in the elimination of an antiepileptic, carbamazepine (CBZ) and an analgesic, diclofenac (DCF) in seven prototype EGSB (Expanded Granular Sludge Bed) reactors on a laboratory scale. The experimentation in the EGSB reactors begins with the start-up and stability of the so-called stage I reactors using sodium acetate as cosubstrate for a concentration of 710.87±3.93 mg/L in terms of COD. Following stages II, III and IV with the dosage of sodium acetate and/or a load of 100,500 and 1000 μg/L of CBZ and DCF respectively, in the seven EGSB models, pausing the dosage of pharmaceutical compounds between each stage; showing instability of the microbial population in the presence of CBZ, unlike DCF for which the microbial population showed a high tolerance during stage II, the above was evidenced in terms of mean removal efficiency of 20.53±5.97%, 22.53±19.15%, 23.88±22.72% and 14.06±10.66% in stage II; 27.01±11.84%, 15.91±5.77%, 24.95±12.83% and 24.13±5.97% in stage III; 3.33±4.35%, 4.02±2.24%, 16.55±3.33% and 7.02±14.33% in stage IV in the EGSB2, EGSB3, EGSB6 and EGSB7 reactors respectively, dosed with CBZ and an average removal efficiency of 98.58±1.82%, 95.58±4.17%, 84.11±34.57% and 79.49±29.88% in stage II; 14.43±11.54%, 20.43±7.90%, 31.22±14.75% and 22.08±9.95% in stage III; 12.42±4.41%, 17.65±10.59%, 27.61±4.81% and 18.87±1.98% in stage IV in the reactors EGSB4, EGSB5, EGSB6, EGSB7 respectively, dosed with DCF, it was also concluded that in the presence of sodium acetate the Reactor efficiency is higher compared to reactors with no co-substrate.