This study aims to find the prevalence of medication non-compliance among schizophrenia inpatients and to compare the relative risks of medication non-compliance with cannabis use disorders (CUDs) versus without CUDs. In addition, this study also examines the odds of medication non-compliance in schizophrenia inpatients with CUDs. This is a retrospective cross-sectional analysis of the nationwide inpatient sample. This sample includes 1,030,949 inpatients (age 18 to 65 years) from 2010 to 2014 with primary ICD-9 diagnoses of schizophrenia and other psychotic disorders, that were further sub grouped based on medication non-compliance. CUDs were recognized using the ICD-9 codes. The prevalence of medication non-compliance was 26% among schizophrenia inpatients. Multivariable analysis revealed that CUD comorbidity was a significant risk factor for medication non-compliance among schizophrenia patients when unadjusted (OR 1.49, 95%CI 1.469–1.503), and association remained significant even after adjusting for covariates (adjusted OR 1.38, 95%CI 1.268–1.489). Comorbid CUD was seen in young adults (18–35 years, 62.4%), males (80.5%), African Americans (54.1%) and low-income families below 25th percentile (48.6%) with personality disorders (10.5%). Medication compliance is a challenge among schizophrenia patients, which has a significant adverse impact on the course of illness. CUD Comorbidity increases the risk of medication non-compliance significantly among schizophrenia patients. In addition to case management, an integrated treatment model to address both substance use disorders and psychosis will translate into better long-term outcomes in schizophrenia patients.