Inappropriate variations in clinical practice are a known cause of poor quality and safety, with variations often associated with nonclinical factors, such as individual differences in cognitive processing. The differential response of physicians to uncertainty may explain some of the variations in resource use and patient experience. To examine the association of physician tolerance for uncertainty with variations in resource use and patient experience. This survey study linked physician survey data (May to June 2019), patient experience survey data (January 2016 to December 2019), and billing data (January 2019 to December 2019) among primary care physicians (PCPs) at Massachusetts General Hospital with at least 10 visits in 2019. The statistical analysis was performed in 2021. The analysis examined associations of PCP tolerance for uncertainty with the tendency to order diagnostic tests, the frequency of outpatient visits, hospital admissions, emergency department visits, and patient experience data (focused on physician communication and overall rating). A 2-stage hierarchical framework was used to account for clustering of patients under PCPs. Binary outcomes were modeled using a hierarchical logistic model, and count outcomes were modeled using hierarchical Poisson or negative binomial models. The analysis was adjusted for patient demographic variables (age, sex, and race and ethnicity), socioeconomic factors (payer and neighborhood income), and clinical comorbidities. Of 217 included physicians, 137 (63.1%) were women, and 174 (80.2%) were adult PCPs. A total of 62 physicians (28.6%) reported low tolerance, 59 (27.2%) reported medium tolerance, and 96 (44.2%) reported high tolerance for uncertainty. Physicians with a low tolerance for uncertainty were less likely to order complete blood cell counts (odds ratio [OR], 0.66; 95% CI, 0.50-0.88), thyroid tests (OR, 0.67; 95% CI, 0.52-0.88), a basic metabolic profile (OR, 0.78; 95% CI, 0.60-1.00), and liver function tests (OR, 0.72; 95% CI, 0.53-0.99) than physicians with a high tolerance for uncertainty. Physicians who reported higher tolerance for uncertainty were more likely to receive higher patient experience scores for listening to patients carefully (OR, 0.65; 95% CI, 0.50-0.83) and higher overall ratings (OR, 0.80; 95% CI, 0.66-0.98) than physicians with medium tolerance. Conversely, no association was found between physician tolerance for uncertainty and patient outpatient visits, hospital admissions, or emergency department visits. In clinical practice, identifying and effectively managing inappropriate variations and improving patient experience have proven to be difficult, despite increased attention to these issues. This study supports the hypothesis that physicians' tolerance for uncertainty is associated with differences in resource use and patient experience. Whether enhancing physicians' tolerance for uncertainty could help reduce unwarranted practice variations, improve quality and patient safety, and improve patient's experience remains to be established.