OBJECTIVES: To analyze the effects of pre-existing substance use on complications in Medicare elderly prostate cancer patients treated with radical prostatectomy. METHODS: We used SEER-Medicare linked database to identify men diagnosed with prostate cancer between 2000 and 2009 and treated with radical prostatectomy, we identified those with a pre-existing diagnosis of substance use (ICD-9 codes: Alcohol dependence syndrome-303.xx, Drug dependence 304.xx and Non-dependent abuse of drugs 305.xx). Seven mutually exclusive complications related to radical prostatectomy (respiratory, cardiac, vascular, wound/bleeding, genitourinary, miscellaneous medical and surgical) were identified in the sixty days post-radical prostatectomy. Number of complications is modeled as a factor of pre-existing substance use, after controlling for socio-demographic and clinical characteristics using Poisson regression. We also analyzed the effects of specific types of substance use on complications. RESULTS: Of the 33,148 men treated with radical prostatectomy, 6.01% had a pre-existing diagnosis of substance use. Complications within sixty days of radical prostatectomy were higher for those with pre-existing substance use (OR=1.34; CI=1.25 - 1.44), compared to those without. In particular, drug dependence had the highest impact on complications (OR= 4.12; CI=2.86- 5.94), compared to alcohol and non-dependent abuse of drugs. CONCLUSIONS: Complications related to radical prostatectomy are significantly affected by pre-existing substance use in elderly prostate cancer patients. Also, this affect varies by type of substance use. Complications are an important indicator of quality of care and thus, our results emphasize the need to for early diagnosis and effective treatment of substance use, especially drug dependence, in elderly prostate cancer patients.