Nitroglycerin is also used medically as a vasodilator to treat heart conditions, such as angina and chronic heart failure. It is one of the oldest and most useful drugs for treating heart disease by shortening or even preventing attacks of angina pectoris. Nitroglycerin comes in forms of tablets, sprays or patches. Nitroglycerin may be able to be used to help destroy prostate cancer.

Nitroglycerin is used for the treatment of angina^[1], acute myocardial infarction^[2], severe hypertension^{[citation needed]}, and coronary artery spasms due to cocaine^{[citation needed]}.

It is useful in decreasing angina attacks, perhaps more so than reversing angina once started, by supplementing blood concentrations of nitric oxide, also called Endothelium-derived relaxing factor, before the structure of NO as the responsible agent was known. This led to the development of transdermal patches of glyceryl trinitrate, providing 24-hour release^[3]. However the effectiveness of glyceryl trinitrate is limited by development of tolerance/tachyphylaxis within 2–3 weeks of sustained use. Continuous administration and absorption (such as provided by daily pills and especially skin patches) accelerate onset of tolerance and limit the usefulness of the agent. Thus glyceryl trinitrate works best when used only short term, pulse dosing. Glyceryl trinitrate is useful for AMI and pulmonary edema^{[citation needed]}, again working best if used quickly, within a few minutes of symptom onset, as a pulse dose^{[citation needed]}. It may also be given as a sublingual or buccal dose in the form of a tablet placed under the tongue or a spray into the mouth for the treatment of an angina attack.^[4]

Glyceryl trinitrate is also used in the treatment of anal fissures, though usually at a much lower concentration than that used for angina treatment.^[5]