Five technological schemes for propionic acid production from raw glycerol were designed, simulated, and economically assessed. Fermentative scenarios considered two different qualities of glycerol: 88 and 98 wt % with concentrations in the fermentation media from 20 to 50 g/L. Raw glycerol (60 wt %) was considered as the feedstock feeding the production process in all cases; then a purification process of raw glycerol up to the required quality was used. Simulation processes were carried out using Aspen Plus, while economic assessments were performed using Aspen Icarus Process Evaluator. Propionic acid recovery and purification processes were based on reactive–extraction with tri-n-octylamine using ethyl acetate as extractant agent. This technology results in energy-intensive processes with total energy consumption ranging from 120.4 to 138.9 MJ/kg. However, further significant improvements could be obtained using energy integration techniques. On the other hand, it was found that the production costs are directly related to the fermentation stage and decrease as follows: (i) increasing the glycerol concentration, (ii) decreasing the glycerol purity, and (iii) increasing the glycerol consumption.