Background: In patients undergoing coronary intervention, different vasodilators are used to prevent the radial artery spasm (RAS). To date, no studies investigated the effect of these vasodilators in blood pressure (BP) reduction. Aim: The study aimed to investigate and compare the effect of vasodilatory medications on BP reduction in patients undergoing transradial coronary angiography procedure. Methods: We consecutively included 300 patients undergoing transradial coronary angiography procedures and randomly assigned them into three equal groups to compare the effect of verapamil (2.5 mg), nitroglycerin (200 μg), and combination (verapamil 2.5 mg with nitroglycerin 200 (μg) was diluted in 5 ml of normal saline and given through radial sheath. Changes in the BP, heart rate (HR), and other clinical parameters were assessed and presented as standardized mean differences (SMD) with 95% confidence intervals (CIs). ANOVA test was performed to analyze the differences in the BP and other clinical parameters between the three groups. Results: Overall, the mean age of the study population was 53.26 years (standard deviation: 9.27), male patients (84%), with dyslipidemia (62.6%), and diabetes (45%). At baseline, the mean systolic BP (SBP) was 150.91 ± 31.66 mmHg, HR (72.34 ± 12.71 beats/min). After the administration of vasodilators, the combination group reduced SBP significantly (SMD: −33.35 [95% CI]: −40.27–−26.42, P < 0.001). There was a statistically significant difference between groups for the SBP ( F [2,296] =3.38, P = 0.035). Verapamil alone showed a significant decrease in the SBP by −27.23 mmHg and diastolic BP by −4.980 mmHg. Conclusion: Intra-arterial administration of verapamil alone showed lower BP reduction compared to the combination of vasodilators. Verapamil could be a safer and effective alternative to prevent RAS with no deleterious effect on BP and HR in patients undergoing transradial coronary angiography.