While comorbidity of serious mental illness (SMI) and substance abuse increases violence risk, less is known about additional effects of multiple substance abuse. By using a check list, data on substance abuse, violence, diagnoses, and Perceived Threat Control Override symptoms (TCO) were extracted from electronic patient files in 146 male patients who were extensive users of acute psychiatric services. Variables that were significant in univariate analysis were entered into a stepwise multivariate regression analysis. Odds ratios for violence increased from 5.3 in patients who abused one substance to 153.4 with the abuse of four or five substances (Step 1). The effect was moderated in Step 2 by having a diagnosis of mood disorder (OR = .17). In Step 3, only a trend indicated that one TCO component, "others control my thoughts and feelings," increased the risk of violence (OR = 3.7). The positive effect sizes for polysubstance abuse were about two times larger in Step 3 than in Step 1. The findings indicate that including the number of abused substances may improve violence risk assessment in patients with SMI.