There is emerging evidence of high mortality rates after the first diagnosis of psychotic disorder. The objective of this study was to estimate the standardized mortality ratio (SMR) in a population-based cohort of individuals with a first diagnosis of schizophrenia-spectrum psychotic disorder (SSD). The cohort included a population-based sample of individuals with a first diagnosis of SSD based on the first diagnosis occurring during hospitalization or in an outpatient setting between 2007 and 2010 in Ontario, Canada. All patients were followed for 5 years after the first diagnosis. The primary outcome was SMR, including all-cause, suicide-related, accidental, and other causes. Between 2007 and 2010, there were 2382 patients in the hospitalization cohort and 11 003 patients in the outpatient cohort. Over the 5-year observation period, 97 (4.1%) of the hospitalization cohort and 292 (2.7%) of the outpatient cohort died, resulting in an SMR of 13.6 and 9.1, respectively. In both cohorts, suicide was the most common cause of death. Approximately 1 in 25 patients with a first diagnosis of SSD during hospitalization, and 1 in 40 patients with a first diagnosis of SSD in an outpatient setting, died within 5 years of first diagnosis in Ontario, Canada. This mortality rate is between 9 and 13 times higher than would be expected in the age-matched general population. Based on these data, timely access to services should be a public health priority to reduce mortality following a first diagnosis of an SSD.