objectives: the first part of this study aims to assess the impact of major depressive disorder (mdd) on cancer survival and to determine whether the impact is modified by the number of other comorbidities in a patient. the second part evaluates the impact of adequate antidepressant refill (aar) on the survival of older cancer patients with mdd. methods: the study used a retrospective cohort design and conducted a population-based study on all adult cancer patients diagnosed in ontario between 2003 and 2013. the cohort was followed until 2018. patients who had a hospital discharge diagnosis of mdd before or during the study period were identified as having depression. for the second part of the study, data on a subset of patients who were ≥ 65 years old at the time of cancer diagnosis and had mdd were analysed. fifteen chronic conditions were included for calculating the number of comorbidities excluding mdd. survival analysis was performed using cox proportional hazards regression. results: among the 453,012 adults diagnosed with cancer, 2% had a hospital diagnosis of mdd. those who had mdd had a higher risk of mortality (adjusted hazard ratio (ahr) 1.58; 95% confidence interval (ci) 1.54-1.63) than those without mdd. in patients with mdd, those with 0-1 comorbidities had 2.55 times (ahr 2.55; 95% ci 2.31-2.81), those with 2-3 comorbidities had 1.85 times (ahr 1.85; 95% ci 1.75-1.95), and those with ≥ 4 comorbidities had 1.44 times (ahr 1.44; 95% ci 1.40-1.49) higher risk of death compared to patients without mdd with similar levels of multimorbidity. there were 4,708 patients who were ≥ 65 years old and had mdd. among patients whose mdd was diagnosed after cancer (n=3,183 (67.6%)), aar was associated with a lower mortality risk (ahr 0.51; 95% ci 0.47-0.55). conclusion: cancer patients without mdd survive longer than those with mdd. older patients with mdd diagnosed after cancer are likely to survive longer if they receive aar.