Twenty-eight coronary artery disease patients with more than 50% stenosis in at least one major coronary artery completed this randomized crossover clinical trial for the comparison of efficacy and safety of Nitrolingual-Spray and nitroglycerin (NTG) tablets. Exercise time was lengthened to 399.1 s (spray) or 408.5 s (tablets), compared to a baseline of 387.3 s. Ischemic burden decreased to about –4.0 mm with both forms, compared to –7.5 mm at baseline (ANOVA: p = 0.003). The ischemic time improved to 137.2 s (spray) or 152.9 s (tablets), compared to 253.4 s at baseline (ANOVA: p = 0.005). Patients taking tablets experienced more episodes of hypotension and/or headache compared to patients taking the spray. Nitrolingual-Spray is as effective and safe as NTG tablets for the treatment of symptomatic coronary heart disease.