A key component of organic bioelectronics is electrolyte-gated organic field-effect transistors (EG-OFETs), which have recently been used as sensors to demonstrate label-free, single-molecule detection. However, these devices exhibit limited stability when operated in direct contact with aqueous electrolytes. Here we demonstrate that ultra-high stability can be achieved using a systematic multifactorial approach. By carefully controlling a set of intricate stability-limiting factors, including contamination and corrosion, we fabricated EG-OFETs with operational stability and lifetime several orders of magnitude higher than the state of the art. Our indacenodithiophene-co-benzothiadiazole (IDTBT) EG-OFETs exhibit operational stability that exceeds 900 minutes in a variety of widely used electrolytes. Moreover, their overall lifetime exceeds two months in ultrapure water and one month in various electrolytes. The devices were not affected by electrical stress-induced trap states, and can remain stable even in voltage ranges where electrochemical doping occurs. To validate the applicability of our stabilized device for biosensing applications, we demonstrate the reliable detection of the protein lysozyme in ultrapure water, and in a physiological sodium phosphate buffer solution for 1500 minutes. Our results show that polymer-based EG-OFETs are a viable architecture not only for short-term but also long-term biosensing applications.