This chapter deals with digital method of calibration for analog integrated circuits as a means of extending its lifetime and reliability, which consequently affects the reliability the analog electronic system as a whole. The proposed method can compensate for drift in circuit's electrical parameters, which occurs either in a long term due to aging and electrical stress or it is rather more acute, being caused by process, voltage and temperature variations. The chapter reveals the implementation of ultra-low voltage on-chip system of digitally calibrated variable-gain amplifier (VGA), fabricated in CMOS 130 nm technology. It operates reliably under supply voltage of 600 mV with 10% variation, in temperature range from − 20 ° C to 85 ° C . Simulations suggest that the system will preserve its parameters for at least 10 years of operation. Experimental verification over 10 packaged integrated circuit (IC) samples shows the input offset voltage of VGA is suppressed in range of 13 μV to 167 μV . With calibration the VGA closely meets its nominally designed essential specifications as voltage gain or bandwidth. Digital calibration is comprehensively compared to its widely used alternative, Chopper stabilization through its implementation for the same VGA.