INTRODUCTION: Patients with transplant-ineligible (TIE) multiple myeloma (MM) have high rates of symptom burden. The aim of this study was to develop and validate a prognostic model to predict symptoms in patients with TIE MM. METHODS: In this population-based, retrospective cohort study, using multiple administrative health care databases linked using a unique encrypted patient identifier in Ontario, Canada, symptoms were identified using the patient self-reported Edmonton Symptom Assessment System (ESAS) at each clinic visit. The primary outcome was the presence of moderate-to-severe (ESAS score 4-10) symptoms (specifically symptoms of pain, tiredness, depression, and impaired well-being) within one year from the index date. Using the entire cohort, a multivariable logistic regression model with baseline covariates was developed to predict the risk of experiencing each of the above symptoms, categorized as moderate to severe within 1 year post-index date. Internal validation of the model was assessed via bootstrap validation methods. RESULTS: A total of 1535 TIE adults with MM met the inclusion criteria. The median age was 75, with 25.2% of patients aged 80 years or older. In the multivariate analysis, baseline symptoms continued to be most associated with future symptom burden. Baseline severe pain (OR 9.84, 95% CI 6.29-15.7) was most associated with patients experiencing moderate-severe pain one year post-index date. Similarly, baseline severe tiredness (OR 17.34, 95% CI 9.00-33.42), baseline severe depression (OR 28.07, 95% CI 15.96-49.38), and baseline severely impaired well-being (OR 4.12, 95% CI 2.30-7.37) were the biggest predictors of patients experiencing moderate-severe tiredness, depression, and impaired well-being, respectively, at one year after the index date. CONCLUSIONS: Patients with MM experience persisting symptoms of pain, tiredness, depression, and impaired well-being, with baseline symptoms being the biggest predictor of future symptom burden.