Many believe a major cause of the epidemic of clinician burnout is poorly designed electronic health records (EHRs). To determine which EHR design and use factors are associated with clinician stress and burnout and to identify other sources that contribute to this problem. This survey study of 282 ambulatory primary care and subspecialty clinicians from 3 institutions measured stress and burnout, opinions on EHR design and use factors, and helpful coping strategies. Linear and logistic regressions were used to estimate associations of work conditions with stress on a continuous scale and burnout as a binary outcome from an ordered categorical scale. The survey was conducted between August 2016 and July 2017, with data analyzed from January 2019 to May 2019. Clinician stress and burnout as measured with validated questions, the EHR design and use factors identified by clinicians as most associated with stress and burnout, and measures of clinician working conditions. Of 640 clinicians, 282 (44.1%) responded. Of these, 241 (85.5%) were physicians, 160 (56.7%) were women, and 193 (68.4%) worked in primary care. The most prevalent concerns about EHR design and use were excessive data entry requirements (245 [86.9%]), long cut-and-pasted notes (212 [75.2%]), inaccessibility of information from multiple institutions (206 [73.1%]), notes geared toward billing (206 [73.1%]), interference with work-life balance (178 [63.1%]), and problems with posture (144 [51.1%]) and pain (134 [47.5%]) attributed to the use of EHRs. Overall, EHR design and use factors accounted for 12.5% of variance in measures of stress and 6.8% of variance in measures of burnout. Work conditions, including EHR use and design factors, accounted for 58.1% of variance in stress; key work conditions were office atmospheres (β̂ = 1.26; P < .001), control of workload (for optimal control: β̂ = -7.86; P < .001), and physical symptoms attributed to EHR use (β̂ = 1.29; P < .001). Work conditions accounted for 36.2% of variance in burnout, where challenges included chaos (adjusted odds ratio, 1.39; 95% CI, 1.10-1.75; P = .006) and physical symptoms perceived to be from EHR use (adjusted odds ratio, 2.01; 95% CI, 1.48-2.74; P < .001). Coping strategies were associated with only 2.4% of the variability in stress and 1.7% of the variability in burnout. Although EHR design and use factors are associated with clinician stress and burnout, other challenges, such as chaotic clinic atmospheres and workload control, explain considerably more of the variance in these adverse clinician outcomes.