There are few studies comparing the outcomes of patients who are treated with oral versus intramuscular antibiotics, corticosteroids, nonsteroidal anti-inflammatory drugs, or vitamin B12. This may lead to confusion about when the intramuscular route is indicated. For example, intramuscular ceftriaxone for Neisseria gonorrhoeae infection and intramuscular penicillin G benzathine for Treponema pallidum infection are the treatments of choice. However, oral antibiotics are the treatment of choice for the outpatient treatment of pneumonia and most other outpatient bacterial infections. Oral corticosteroids are as effective as intramuscular corticosteroids and are well-tolerated by most patients. High daily doses of oral vitamin B12 with ongoing clinical surveillance appear to be as effective as intramuscular treatment. Few data support choosing intramuscular ketorolac over an oral nonsteroidal anti-inflammatory drug unless the patient is unable to tolerate an oral medication. For other indications, the intramuscular route should be considered only when the delivery of a medication must be confirmed, such as when a patient cannot tolerate an oral medication, or when compliance is uncertain.