Objective: To estimate the highest burden of treatment beyond which patients with chronic conditions consider their current investments of time and effort in health care unsustainable. Patients and Methods: We used data collected between January 1, 2017 and October 1, 2018 in the Community of Patients for Research (ComPaRe), an ongoing e-cohort of adult patients with chronic conditions in France. We matched participants’ answers to the Treatment Burden Questionnaire (TBQ) and to a Yes/No anchor question: “Think about all the things you do to care for yourself. Do you think you could continue investing the same amount of time, energy, and money in your health care lifelong?” We defined the Patient Acceptable Symptom State (PASS) for the burden of treatment as the TBQ score below which 75% of patients reported an acceptable burden state. Results: We analyzed data for 2413 patients (1781 [73.8%] women, 1248 [51.7%] multimorbid, median age: 48 (interquartile range, 36-59] years) enrolled in ComPaRe. Of these, 38% (917 of 2413) reported that they would be unable to continue the same investment of energy, time, and money in health care lifelong. The PASS for the burden of treatment was at 39% of the maximal score (ie, TBQ score = 59/150; 95% CI, 52-64) Using these results, clinicians can detect patients at risk for becoming overwhelmed by their medical care by identifying patients with TBQ scores of 59 or higher. Conclusion: About 40% of patients with chronic conditions report being unable to sustain current investments of energy, time, and money in health care lifelong. The PASS for treatment burden provides a practical yardstick to help clinicians and researchers interpret scores for burden of treatment.