OBJECTIVE We reviewed our management of indeterminate urinary cytologies to determine which patients warrant urological evaluation. Our goal was to develop a cost-effective evaluation scheme that detects the most cancers. METHODS We analyzed case histories of 389 patients with indeterminate urinary cytology who had undergone complete urological evaluations. Upper urinary tract imaging and cystoscopy were required to exclude malignancy, and tissue biopsy results were recorded in all individuals diagnosed with cancer. Multivariate analysis was used to assess the significance of clinical factors that would suggest the necessity of complete urinary system evaluation. Marginal cost-effectiveness rates were applied to various clinical scenarios. RESULTS Of 389 patients 60 (15%) had urinary tract malignancy. A history of urothelial malignancy and hematuria were the only significant factors that suggested complete evaluation was necessary. If smoking history were included 59 of the 60 malignancies would have been detected. CONCLUSIONS Patients with indeterminate urinary cytology who are nonsmokers and have neither hematuria nor a history of urothelial cancer are at low risk for malignancy and do not warrant complete evaluation.