Background: Management of complicated intra-abdominal infections (cIAIs) includes broad-spectrum antimicrobial coverage and commonly includes vancomycin for the empiric coverage of methicillin-resistant Staphylococcus aureus (MRSA). Ideally, culture-guided de-escalation follows to promote robust antimicrobial stewardship. This study assessed the impact and necessity of vancomycin in cIAI treatment regimens. Patients and Methods: A post hoc analysis of the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial was performed. Patients receiving piperacillin-tazobactam (P/T) and/or a carbapenem were included with categorization based on use of vancomycin. Univariate and multivariable analyses evaluated effects of including vancomycin on individual and the composite of undesirable outcomes (recurrent IAI, surgical site infection [SSI], or death). Results: The study cohort included 344 patients with 110 (32%) patients receiving vancomycin. Isolation of MRSA occurred in only eight (2.3%) patients. Vancomycin use was associated with a similar composite outcome, 29.1%, vs. no vancomycin, 22.2% (p = 0.17). Patients receiving vancomycin had (mean [standard deviation]) higher Acute Physiology and Chronic Health Evaluation II scores (13.1 [6.6] vs. 9.4 [5.7], p < 0.0001), extended length of stay (12.6 [10.2] vs. 8.6 [8.0] d, p < 0.001), and prolonged antibiotic courses (9.1 [8.0] vs. 7.1 [4.9] d, p = 0.02). After risk adjustment in a multivariate model, no significant difference existed for the measured outcomes. Conclusions: This post hoc analysis reveals that addition of vancomycin occurred in nearly one third of patients and more often in sicker patients. Despite this selection bias, no appreciable differences in undesired outcomes were demonstrated, suggesting limited utility for adding vancomycin to cIAI treatment regimens.