PURPOSE: Minnesota's medical cannabis program is unique, in that it routinely collects patient-reported scores on symptoms. This article focuses on changes in symptom severity reported by patients with cancer during their first 4 months of program participation. MATERIALS AND METHODS: Patients with cancer in Minnesota's medical cannabis program reported symptoms (anxiety, lack of appetite, depression, disturbed sleep, fatigue, nausea, pain, and vomiting) at their worst over the last 24 hours before each medical cannabis purchase. Baseline scores on each of the eight symptoms were statistically compared with the average symptom scores reported in the first 4 months of program participation. Symptom scores were also calculated as percent change from baseline, with patients achieving and maintaining at least a 30% reduction in symptoms reported in this article. Patients also reported intensity of adverse effects. RESULTS: A significant reduction in scores was found across all symptoms when comparing baseline scores with the average score submitted within the first 4 months of program participation (all Ps < .001). The proportion of patients achieving 30% or greater symptom reduction within the first 4 months of program participation varied from 27% (fatigue) to 50% (vomiting), with a smaller proportion both achieving and maintaining those improvements. Adverse effects were reported in a small proportion of patients (10.5%). CONCLUSION: Patients with cancer enrolled in Minnesota's medical cannabis program showed significant reduction across all eight symptoms assessed within 4 months of program participation. Medical cannabis was well tolerated, and some patients attained clinically meaningful and lasting levels of improvement.