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Background and Aims: We hypothesized that maintaining a patient on moderate–high doses of potent inhalational agent for greater than 30 min during the post-bypass period would be an independent predictor of initiation and usage of either inotropic and/or vasopressor infusions. Setting and Design: This study is a retrospective design and approved by the institutional review board. The setting was a single-center, academic tertiary care hospital in Detroit, Michigan. Materials and Methods: Three-hundred, ninety-seven elective cardiac surgery patients were identified for chart review. Electronic medical records were reviewed to collect demographics and perioperative data. Statistics used include a propensity score regression adjusted analysis utilizing logistic regression models and a multivariable model. Results: A propensity score regression adjusted analysis was performed and then applied in both univariate and multivariate logistic regression models with a p value of <0.05 reaching statistical significance. Fifty-six percent of the participants had an exposure of greater than 30 min of a minimum alveolar concentration of isoflurane greater than 0.5 (ETISO ≥ 0.5MAC, 30 min) in the post-bypass period. After adjusting for propensity score, this was found to be a significant predictor of inotrope and/or vasoconstrictor use post-bypass (OR 2.49, 95% CI 1.15–5.38, p = 0.021). In the multivariate model, pulmonary hypertension (OR 5.9; 95% CI 1.33–26.28; p = 0.02), Euroscore II (2.73; 95% CI 1.35–5.5; p = 0.005), and cardiopulmonary bypass hours (OR 1.86; 95% CI 1.02–3.4; p = 0.042) emerged as significant. Conclusions: This study showed that an ETISO ≥ 0.5MAC, 30 min exposure during the immediate post-bypass period during elective cardiac surgery was an independent predictor of a patient being started on inotrope or vasoconstrictor infusions. Further research should consider a prospective design and examine depth of anesthesia during the post-bypass period.