Misiaszek returned to action in 2021 with the Single-A Lynchburg Hillcats, High-A Lake County Captains, and Double-A Akron RubberDucks. In 32 appearances split between the three affiliates, he pitched to a cumulative 4-2 record and 3.47 ERA with 87 strikeouts and one save across 62+1⁄3 innings pitched.[5] Misiaszek split the 2022 campaign between Akron and the Triple-A Columbus Clippers, logging a combined 5-2 record and 2.04 ERA with 90 strikeouts across 61+2⁄3 innings pitched.[6]
Misiaszek underwent Tommy John surgery in June 2023, causing him to miss the entirety of the season as a result.[7] Upon returning in late 2024, he recorded a 4-1 record and 3.80 ERA with 29 strikeouts in 21 games for Columbus and the rookie-level Arizona Complex League Guardians.[8] Misiaszek made 23 appearances out of the bullpen for Columbus in 2025, but struggled to a 7.31 ERA with 27 strikeouts and two saves across 28+1⁄3 innings pitched. Misiaszek was released by the Guardians organization on August 11, 2025.[9]