Objective To examine associations among substance use disorder (SUD) and measures of length of stay (LOS) and non‐psychiatric medical comorbidity (MEDCO) in older‐adult inpatients with serious mental illness (SMI), hypothesizing SUD would be related to worse clinical outcomes. Methods A cross‐sectional study analyzed medical records from 2010 to 2016 of 7258 inpatients with SMI ≥ age 50, obtained from a 274‐bed psychiatric hospital. Descriptive analyses examined prevalence rates for SUD status (+/−), individual drug classes, and total number of SUDs (polysubstance use disorders). Regression models examined the influence of 2 independent variables of interest: (1) SUD status (+/−) and (2) type of SUD (ie, specific drug), controlling for demographic factors and additional (non‐SUD) psychiatric disorders. Two dependent (outcome) variables were examined: LOS and MEDCO. Results The overall SUD rate was 26%; cocaine was the most common SUD (≈ 10%). SUD status and additional (non‐SUD) psychiatric diagnoses were significantly associated with longer LOS (both P < 0.001). For individual SUDs, cocaine, marijuana, opiates, and alcohol were all significantly associated with LOS (all P < 0.01). SUD status, age, sex, admission status, and race were significantly associated with MEDCO (all P < 0.002). For individual SUDs, barbiturates, opiates, and alcohol were all significantly associated with MEDCO (P < 0.01). Conclusions The prevalence of SUD in this sample underscores concerns related to treating older adults presenting providers with comorbid SUD and SMI. This combination may increase the burden and complexity of care, warranting further investigation into mechanisms and long‐term consequences.