The Clavien-Dindo Classification (CDC) lacks a combined score of multiple complications in one patient. The comprehensive complication index (CCI) circumvents this problem making it a valuable instrument to optimize quality control. We aimed to introduce and validate CCI in the treatment of urolithiasis. 60 day postoperative complications of 327 consecutive patients undergoing percutaneous nephrolitholapaxy (PNL) and ureterorenoscopy (URS) between 2017 and 2019 were retrospectively assessed and graded according to CDC. CCI was calculated for each patient. Overall morbidity scores of CCI and CDC were compared. Correlation analyses between the two scores and length of hospital stay (LOS) were performed. A multivariate analysis was performed to identify predictive factors for complications. Sample size calculation for an imaginary clinical trial was compared between CCI and CDC. A significant difference in overall morbidity between CCI and CDC was revealed for PNL (p < 0.001) and URS (p = 0.001). There was no statistically significant difference in comparing correlations between cumulative CCI and LOS versus non-cumulative CDC and LOS for both cohorts. Operating time > 90 min, maximum stone size, positive preoperative urine culture and PNL type (p < 0.001) were predictive factors for postoperative complications in PNL, while urine culture (p = 0.02) was for URS. Sample size calculation based on CCI resulted in a significant reduction of required patients for PNL (- 48%) and URS (- 84%) compared to CDC. CCI could successfully be validated in endourological stone treatment with the advantage of assessing complications in their entirety compared to CDC. CCI can significantly reduce the required sample size in future clinical trials.