Abstract Background Although widely accepted for adults, the safety of outpatient parenteral antimicrobial therapy (OPAT) in very old patients has not been examined. Methods Nonagenarians (age ≥90 years) discharged from the hospital on OPAT over a 5-year period were identified from the Cleveland Clinic OPAT Registry. Three matched controls (<90 years) were selected for each nonagenarian. Times to OPAT-related emergency department (ED) visit and OPAT-related readmission were compared across the 2 groups in multivariable subdistribution proportional hazards competing risks regression models. Incidence of adverse drug events and vascular access complications were compared using negative binomial regression. Results Of 126 nonagenarians and 378 controls, 7 were excluded for various reasons. Among the remaining 497 subjects, 306 (62%) were male, 311 (63%) were treated for cardiovascular or osteoarticular infections, and 363 (73%) were discharged to a residential health care facility. The mean (SD) ages of nonagenarians and controls were 92 (2) and 62 (16) years, respectively. Compared with matched controls, being a nonagenarian was not associated with increased risk of OPAT-related ED visit (hazard ratio [HR], 0.77; 95% CI, 0.33–1.80; P = .55), OPAT-related readmission (HR, 0.78; 95% CI, 0.28–2.16; P = .63), adverse drug event from OPAT medications (incidence rate ratio [IRR], 1.00; 95% CI, 0.43–2.17; P = .99), or vascular access complications (IRR, 0.66; 95% CI, 0.27–1.51; P = .32). Nonagenarians had a higher risk of death overall (HR, 2.64; 95% CI, 1.52–4.58; P < .001), but deaths were not from OPAT complications. Conclusions Compared with younger patients, OPAT in nonagenarians is not associated with higher risk of OPAT-related complications. OPAT can be provided as safely to nonagenarians as to younger patients.