IMPORTANCE Emergency department visits and hospitalizations after starting systemic therapy for cancer are frequent, undesirable, and costly. A score to quantify the risk of needing acute care can inform decision-making and facilitate the development of preventive interventions. OBJECTIVE To develop and validate a score to predict early use of acute care after initiating systemic therapy for cancer. DESIGN, SETTING, AND PARTICIPANTS A retrospective population-based cohort study was conducted between July 1, 2014, and June 30, 2015. Patients with cancer were eligible if they started a new systemic therapy for cancer, regardless of line of therapy. A total of 12 162 patients in Southwestern Ontario, Canada, formed the development cohort and 15 845 patients in Northeastern Ontario formed the validation cohort. Data analysis was conducted from December 1, 2016, to August 10, 2019. EXPOSURES The Prediction of Acute Care Use During Cancer Treatment (PROACCT) score was created based on logistic regression in the development cohort. Combinations of cancer type and regimens were grouped into quintiles based on risk of needing acute care. The score was assessed in the validation cohort. MAIN OUTCOMES AND MEASURES At least 1 emergency department visit or hospitalization within 30 days after starting systemic therapy for cancer identified from administrative databases. RESULTS Among the 12 162 patients in the development cohort, 6903 were women and 5259 were men (mean [SD] age, 62.9 [12.6] years); among the 15 845 patients in the validation cohort, 9025 were women and 6820 were men (mean [SD] age, 62.9 [12.6] years). Use of acute care occurred within 30 days after initiation of systemic therapy in 3039 patients (25.0%) in the development cohort and 4212 patients (26.6%) in the validation cohort. Three characteristics predicted early use of acute care and formed the PROACCT score: combination of cancer type and treatment regimen, age, and emergency department visits in the prior year (C statistic, 0.67; 95% CI, 0.66-0.69; P < .001). Other characteristics including patient-reported symptoms did not improve performance. In the validation cohort, the PROACCT score was associated with use of acute care (odds ratio per point increase, 1.22; 95% CI, 1.20-1.24; P < .001), had a C statistic of 0.61 (95% CI, 0.60-0.62; P < .001), was reasonably calibrated, and provided net benefit in decision curve analysis. CONCLUSIONS AND RELEVANCE The PROACCT score predicted the risk of early use of acute care in patients starting systemic treatment for cancer and could be incorporated at the point of care to select patients for preventive interventions. Future studies should validate the PROACCT score in other settings.