Systems and methods for injecting a drug and detecting tissue induced back pressure are disclosed. A drug delivery system may include a reservoir filled or fillable with a drug, an administration member connected or connectable in fluid communication with the reservoir, a drive assembly, and a pressure sensor. The administration member may be configured for insertion into and subsequently retraction from a patient. The drive assembly may be configured to urge the drug from the reservoir to deliver a dose of the drug to the patient via the administration member. The pressure sensor may be configured to detect tissue back pressure during use of the drug delivery system, including after dose completion and prior to retraction of the administration member. The drug delivery system may be controlled in a manner that accounts for the tissue back pressure measurement.