In percutaneous intervention for treatment of coronary plaques, guidewire navigation is a primary procedure for stent delivery. Steering a flexible guidewire within coronary arteries requires considerable training, and the non-linearity between the control operation and the movement of the guidewire makes precise manipulation difficult. Here, we introduce a deep reinforcement learning (RL) framework for autonomous guidewire navigation in a robot-assisted coronary intervention. Using Rainbow, a segment-wise learning approach is applied to determine how best to accelerate training using human demonstrations, transfer learning, and weight initialization. ‘State’ for RL is customized as a focus window near the guidewire tip, and subgoals are placed to mitigate a sparse reward problem. The RL agent improves performance, eventually enabling the guidewire to reach all valid targets in ‘stable’ phase. Our framework opens a new direction in the automation of robot-assisted intervention, providing guidance on RL in physical spaces involving mechanical fatigue.