Abstract Purpose To validate the comprehensive complication index (CCI) for mini-percutaneous nephrolithotomy (mPCNL). Methods Data from 287 patients who underwent mPCNL were analyzed. Complications after mPCNL were classified using both the CCI and the Clavien–Dindo classification (CDC). Descriptive statistics and linear/logistic regression analyses detailed the association between clinical predictors and mPCNL outcomes. Results After mPCNL, 83 (28.9%) patients had complications, of which 12 (4.2%) patients with multiple complications had a higher CCI score compared to the traditional CDC system accounting only for the highest grade. The CCI enabled a more accurate prediction of length of stay (LOS) than CDC (CCI: r = 0.32; p < 0.01 vs. CDC: r = 0.26; p = 0.01). Patients with multiple complications had higher stone volume (p = 0.02), longer operative time and LOS (all p < 0.01). A higher rate of post-operative hospital readmission (33.3% vs. 9.9%, p = 0.02) and lower rate of stone free (33.3% vs. 64.7%, p = 0.04) were found in patients with multiple complications than in those with single complication. Linear regression analysis revealed that multiple complications were associated with longer LOS (p < 0.001) after accounting for BMI and stone volume. Similarly, having multiple complications was associated with fivefold higher risk of readmission (p = 0.02). Conclusion The CCI is a valuable metric for assessing post-operative complications after mPCNL. The cumulative CCI is a better predictor of LOS than the CDC for mPCNL. Minor complications not captured by the highest CDC score are relevant since patients with multiple complications have longer LOS and higher rate of readmission than those with single ones.