Objective: To identify specific comorbidities within the Charlson Comorbidity Index (CCI) that are associated with increased complication rates after robot-assisted partial nephrectomy (RAPN). Patients and Methods: After institutional review board approval, a consecutive series of 641 patients undergoing RAPN were retrospectively identified. Perioperative complications were defined and classified using the Clavien grading system. Fisher's exact test or chi-square test was performed to evaluate the association of individual comorbidities with perioperative complications. Logistic regression was used for multivariable analysis to adjust for other non-CCI comorbidities and tumor-specific and patient-specific characteristics. Results: Of the 641 patients undergoing RAPN, complications occurred in 67 patients (10.5%), including 10 (14.9%), 28 (41.8%), 20 (29.9%), 5 (7.5%), and 4 (6.0%) patients with Clavien grade 1, 2, 3a, 3b, and 4 complications, respectively. Cerebrovascular disease [odds ratio 3.01 (95% confidence interval [CI] 1.10, 8.26) p = 0.03] and chronic obstructive pulmonary disease [COPD; 3.12 (1.24, 7.89) p = 0.02] predicted complications in multivariable analysis of clinicopathologic characteristics, including all CCI and non-CCI comorbidities. In additional modeling with only CCI comorbidities, similar results were observed, with cerebrovascular disease [2.93 (1.04, 7.56) p = 0.04] and COPD [2.69 (1.04, 6.28) p = 0.04] as the only two significant variables. No other variables reached statistical significance in either model, including nephrometry score or estimated blood loss (p > 0.50 for both). COPD predicted major complications (Clavien grade 3 or 4) in multivariable analysis [3.19 (1.07, 9.48) p = 0.04]. Conclusions: Cerebrovascular disease and COPD predict perioperative RAPN complications after RAPN. Identification of patients with these comorbidities preoperatively may afford improved counseling and risk stratification.