Background: Several studies have implied that the time of radiation exposure for patients and operators during the transradial approach for coronary angiography (TRA) is associated with the use of different guidewire or catheter and operator's finesse. This study aimed to assess the effects of non-hydrophilic or hydrophilic guidewire and operator expertise on fluoroscopy time and procedure time of TRA and further effects on the procedure safety. Methods: A total of 1035 consecutive patients undergoing TRA were recruited prospectively and respectively divided into non-hydrophilic guidewire and hydrophilic guidewire group, or well-experienced group and less-experienced group. The primary endpoints were fluoroscopy time and procedure time. Secondary endpoints included contrast volume, cost, guidewire exchange, switchover and complications. Results: TRA by non-hydrophilic guidewire group showed shorter fluoroscopy time and procedure time compared with hydrophilic guidewire group, similar results were found between well-experienced group and less-experienced group. Moreover, using of non-hydrophilic guidewire significantly reduced the incidence of hematoma and abnormal guidewie advancement, well-experienced group showed less dosage of contrast volume, lower incidence of radial artery spasm and frequency of guidewire exchange. Conclusions: TRA by non-hydrophilic guidewire and well-experienced operator can decrease radiation exposure of patients and operators through reducing the fluoroscopy time and procedure time and further increase procedure safety. These will contribute to the optimization of TRA procedure and promote its widely application.