Background: Symptom distress in patients toward the end of life can change rapidly. Family caregivers have the potential to help patients manage those symptoms, as well as their own stress, if they are equipped with the proper resources. Electronic health (eHealth) systems may be able to provide those resources. Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could.; Objective: The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient's symptoms, as reported by a family caregiver.; Methods: A pooled analysis from two randomized clinical trials (NCT00214162 and NCT00365963) compared outcomes at 12 months for two unblinded groups: a control group (Comprehensive Health Enhancement Support System [CHESS]-Only) that gave caregivers access to CHESS, an online support system, and an experimental group (CHESS+CR [Clinician Report]), which also had CHESS but with a CR that automatically alerted clinicians if symptoms exceeded a predetermined threshold of severity. Participants were dyads (n=235) of patients with advanced lung, breast, or prostate cancer and their respective family caregivers from 5 oncology clinics in the United States of America. The proportion of improved patient threshold symptoms was compared between groups using area-under-the-curve analysis and binomial proportion tests. The proportion of threshold symptoms out of all reported symptoms was also examined.; Results: When severe caregiver-reported symptoms were shared with clinicians, the symptoms were more likely to be subsequently reported as improved than when the symptoms were not shared with clinicians (P<.001). Fewer symptom reports were completed in the group of caregivers whose reports went to clinicians than in the CHESS-Only group (P<.001), perhaps because caregivers, knowing their reports might be sent to a doctor, feared they might be bothering the clinician.; Conclusions: This study suggests that an eHealth system designed for caregivers that alerts clinicians to worrisome changes in patient health status may lead to reduced patient distress.; Trial Registration: Clinicaltrials.gov NCT00214162; https://clinicaltrials.gov/ct2/show/NCT00214162 (Archived by WebCite at http://www.webcitation.org/6nmgdGfuD) and Clinicaltrials.gov NCT00365963; https://clinicaltrials.gov/ct2/show/NCT00365963 (Archived by WebCite at http://www.webcitation.org/6nmh0U8VP).; ©David H Gustafson, Lori L DuBenske, Amy K Atwood, Ming-Yuan Chih, Roberta A Johnson, Fiona McTavish, Andrew Quanbeck, Roger L Brown, James F Cleary, Dhavan Shah. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.11.2017.