Background Several contemporary risk stratification tools are now being used since the development of the Charlson Comorbidity Index (CCI) in 1987. The purpose of this systematic review and meta-analysis was to compare the utility of commonly used co-morbidity indices in predicting surgical outcomes. Methods A comprehensive review was performed to identify studies reporting an association between a pre-operative co-morbidity measurement and an outcome (30-day/in-hospital morbidity/mortality, 90-day morbidity/mortality, and severe complications). Meta-analysis was performed on the pooled data. Results A total of 111 included studies were included with a total cohort size 25,011,834 patients. The studies reporting the 5-item Modified Frailty Index (mFI-5) demonstrated a statistical association with an increase in the odds of in-hospital/30-day mortality (OR:1.97,95%CI: 1.55–2.49, p  < 0.01). The pooled CCI results demonstrated an increase in the odds for in-hospital/30-day mortality (OR:1.44,95%CI: 1.27–1.64, p  < 0.01). Pooled results for co-morbidity indices utilizing a scale-based continuous predictor were significantly associated with an increase in the odds of in-hospital/30-day morbidity (OR:1.32, 95% CI: 1.20–1.46, p  < 0.01). On pooled analysis, the categorical results showed a higher odd for in-hospital/30-day morbidity (OR:1.74,95% CI: 1.50–2.02, p  < 0.01). The mFI-5 was significantly associated with severe complications (Clavien-Dindo ≥ III) (OR:3.31,95% CI:1.13–9.67, p  < 0.04). Pooled results for CCI showed a positive trend toward severe complications but were not significant. Conclusion The contemporary frailty-based index, mFI-5, outperformed the CCI in predicting short-term mortality and severe complications post-surgically. Risk stratification instruments that include a measure of frailty may be more predictive of surgical outcomes compared to traditional indices like the CCI.