Purpose: This retrospective observational study investigated the efficacy and safety of vancomycin to treat patients aged 80 years and older. In particular, the associations between vancomycin trough concentration (VTC) and treatment outcomes or nephrotoxicity were explored. Patients and Methods: Patients aged >= 80 years had received >= 3 vancomycin treatments and >= 1 detection of VTC. Treatment outcomes were defined as success or failure. Nephrotoxicity was considered an increase in serum creatinine >= 44.2 mmol/L, or 50% above baseline, for >= 2 consecutive days. Univariate and multivariate analyses were performed to identify risk factors for treatment failure and nephrotoxicity. Results: Of 349 patients, 120 (34.4%) experienced treatment failure. For patients with VTCs at <10, 10-15, 15-20, and >= 20 mu g/mL, the clinical response rates were, respectively, 77.8, 77.0, 80.5, and 61.0%; the 30-day mortality rates were 2.8, 15.0, 15.3, and 37.8%; and the rates of persistent bacteremia were 16.7, 12.4, 11.9, and 11.0%. The multivariate analysis indicated that blood urea nitrogen >= 11 g/dL and heart failure were independently associated with treatment failure; but not VTC (P = 0.004, 0.016, 0.828, respectively). During vancomycin treatment, 42 (12.0%) patients experienced nephrotoxicity with recovery time 7.5 +/- 4.5 days. Fewer than half of patients with nephrotoxicity recovered after suspending vancomycin application. The variables found independently associated with increased nephrotoxicity were: VTC >= 15 mu g/mL; treatment duration >= 15 d; and concomitant aminoglycosides administration (P = 0.024, 0.035, 0.029). Conclusion: In patients aged 80 years and older, elevated VTC level was not associated with favorable treatment outcomes. Patients with VTC >= 20 mu g/mL appear to suggest a worsened prognosis compared with lower VTCs. The risk of nephrotoxicity increases with elevated VTC, longer treatment time, and concomitant aminoglycoside administration.