Background: In this paper, an ultra-high gain DC-DC converter (UHGC) which provides a very high voltage conversion ratio value of 21.11 is described. Methods: The proposed UHGC is synthesized from a two-phase interleaved quadratic boost converter (IQBC). The voltage gain of the IQBC is further extended by using the voltage-lift technique. To meet the standard DC voltage level of 380 V across the load terminals, the output of the voltage-lifted IQBC is cascaded to a conventional boost converter (CBC). By operating the switches located in the IQBC stage with a duty ratio of 0.5 and 180° phase-shift, the source current ripples are nullified. Besides drawing a smooth and ripple-free current from the input, the converter's voltage gain is adjusted by varying the duty ratio of the switch employed in the CBC stage. Results: The proposed gain extension concept is practically validated by conducting experiments on 18-380 V, 150 W prototype converter. Under practical conditions, the proposed converter operates at full-load efficiency of 94.7%. Moreover, due to the proposed gain enhancing technique, the two switches employed in the IQBC stage are subjected to low voltage stress levels which are 18.95% of the output voltage. By employing a simple closed-loop control technique, the output voltage is regulated to remain constant at 380 V despite variations in line voltage and load current magnitudes. Conclusion: The proposed UHGC possesses some advantageous features like (i) high voltage gain capability, (ii) ability to draw smooth and continuous (ripple-free) current from the input, (iii) flexible structure which provides the required high voltage gain while drawing smooth current from the source and (iv) ability to quickly regulate the output voltage using simple closed-loop control. Thus, the proposed UHGC is an appropriate choice for integrating the input PV source to a common DC bus or microgrid. © 2020 John Wiley & Sons Ltd