14C autoradiography is a well established technique for structural and metabolic analysis of cells and tissues. The most common detection medium for this application is ﬁlm emulsion, which offers unbeatable spatial resolution due to its ﬁne granularity but at the same time has some limiting drawbacks such as poor linearity and rapid saturation. In recent years several digital detectors have been developed, following the technological transition from analog to digital-based detection systems in the medical and biological ﬁeld. Even so such digital systems have been greatly limited by the size of their active area (a few square centimeters), which have made them unsuitable for routine use in many biological applications where sample areas are typically ∼ 10– 100 cm2 . The Multidimensional Integrated Intelligent Imaging (MI3-Plus) consortium has recently developed a new large area CMOS Active Pixel Sensor (12.8cm × 13.1 cm). This detector, based on the use of two different pixel resolutions, is capable of providing simultaneously low noise and high dynamic range on a wafer scale. In this paper we will demonstrate the suitability of this detector for routine beta autoradiography in a comparative approach with widely used ﬁlm emulsion.