Vancomycin and daptomycin are often used in outpatient parenteral antimicrobial therapy for gram-positive coverage. Vancomycin's narrow therapeutic window poses challenges. We retrospectively assessed acute kidney injury (AKI) and other adverse drug events in outpatient parenteral antimicrobial therapy patients receiving vancomycin or daptomycin at home after hospital discharge. Among 191 patients included, AKI was the most common adverse drug event. Early antibiotic discontinuation and AKI were more frequent in the vancomycin group. Vancomycin use (odds ratio [OR], 4.57; 95% confidence interval [CI], 1.02-20.51); p = 0.04], female sex (OR, 3.28; 95%CI, 1.41-7.67; P < .01), and longer hospitalization (OR, 1.06; 95%CI, 1.01-1.11; P = .02] independently predicted moderate-to-severe AKI. In the vancomycin group, trough concentrations increased after discharge, and were higher in female compared to male patients, and in those who developed moderate-to-severe AKI compared to those who did not. Female sex (OR, 8.37; 95%CI, 2.35-29.82; P < .01) and higher concentrations (OR, 1.12; 95%CI, 1.05-1.19; P < .01) predicted moderate-to-severe AKI in patients receiving vancomycin. In conclusion, premature antibiotic discontinuations and nephrotoxicity are more frequent in patients treated at home with vancomycin compared to daptomycin. Among patients receiving vancomycin, plasma concentrations increased after hospital discharge and predicted moderate-to-severe AKI. Women had higher vancomycin concentrations and higher risk for AKI.