This paper investigates the recovery of methanol from the propylene oxide (PO)/methanol/water mixture using reactive distillation (RD). The mixture presents a challenge due to the azeotrope formation between PO and methanol. To overcome this challenge, three RD scenarios, designated as Case 1, Case 2, and Case 3, are proposed. The primary principle underlying these cases is leveraging a reaction between PO and water, resulting in the production of propylene glycol (PG). This reaction consumes PO and thus eliminates the PO-methanol azeotrope, and reduces reboiler duty via the release of reaction heat. Case 1 utilizes one reactive distillation column (RDC) and one conventional distillation column (CDC) to recover methanol while reducing a quarter of the water content via the PO-water reaction. High purity methanol is obtained in the RDC distillate, while high purity PG is collected at the bottom of the CDC. Likewise, Case 2 follows the same approach as Case 1, with an additional PO stream to halve the water content. On the other hand, Case 3 employs a single RDC with a greater additional PO stream to react with all water content in the mixture, yielding high purity methanol at the distillate and PG at the bottom. These cases are simulated using Aspen Plus software, and their designs are optimized to minimize the total annual cost (TAC). The results are compared to a base case, represented by the side-stream extractive distillation (SSED) method. Cases 1, 2, and 3 demonstrate TAC reductions of 7.8 %, 27.7 %, and 60 %, respectively, compared to the base case. Additionally, the PG produced by the PO-water reaction presents opportunities for generating extra profit of 6.356 × 107 $ a−1, 7.248 × 107 $ a−1, and 8.98 × 107 $ a−1 in Cases 1, 2, and 3, respectively. Given the financial benefits observed in each case, these configurations may serve as attractive alternative methods for methanol recovery from the PO/methanol/water mixture.