Introduction Cognitive impairment in schizophrenia and schizoaffective disorder is a major determinant of disability. This study explored the relationships among cognitive functioning, clinical symptoms, overall functionality, and demographic characteristics. Methods This was a post hoc analysis of a 52-week, prospective, randomized, double-blind study (N=323) comparing 2 doses of risperidone long-acting injectable (RLAI) in stable subjects with schizophrenia or schizoaffective disorder. Cognitive evaluations were performed and standardized using a healthy age- and sex-matched comparison group. Simple and multiple regression models were used to identify relationships among neurocognitive composite scores (NCS), clinical symptom end points (Positive and Negative Syndrome Scale [PANSS] total and factor scores), overall functionality (Personal and Social Performance [PSP] score), and demographics. Results A simple regression model identified significant relationships between the NCS at end point and PANSS total score, PANSS disorganized thoughts factor score, functioning (PSP) and age. A 1-point decrease on PANSS total score and PANSS disorganized thoughts factor score corresponded to an increase in NCS of 0.126-point, and 0.81-point increases, respectively. A 1-point increase on the PSP corresponded to a 0.186-point increase in the NCS T-score. Among the demographic variables, only age correlated significantly with cognition (10-year increase in age corresponded to 1.1-point decrease in NCS T-score) in a multiple regression model. Conclusion Improved cognition was associated with beneficial changes in functional status and clinical symptoms (particularly disorganization symptoms) in subjects with schizophrenia/schizoaffective disorder. Older subjects showed less overall cognitive improvement. Improved cognitive and functional outcome is correlated with symptom improvements in RLAI-treated patients with schizophrenia.