BACKGROUND: Although intrinsic motivating factors play important roles in physician well-being and productivity, most studies have focused on extrinsic motivating factors such as salary and work environment. OBJECTIVE: To examine the association of intrinsic motivators with physicians' career satisfaction, life satisfaction, and clinical commitment, while accounting for established extrinsic motivators as well. DESIGN AND PARTICIPANTS: A nationally representative survey of 2000 US physicians, fielded October to December 2011. MAIN MEASURES: Outcome variables were five measures of physician well-being: career satisfaction, life satisfaction, high life meaning, commitment to direct patient care, and commitment to clinical practice. Primary explanatory variables were sense of calling, personally rewarding hours per day, meaningful, long-term relationships with patients, and burnout. Multivariate logit models with survey design provided nationally representative individual-level estimates. KEY RESULTS: Among 1289 respondents, 85.8% and 86.5% were satisfied with their career and life, respectively; 88.6% had high life meaning; 54.5% and 79.5% intended to retain time in direct patient care and continue clinical practice, respectively. Sense of calling was strongly positively associated with high life meaning (odds ratio [OR] 5.14, 95% confidence interval [95% CI] 2.87-9.19) and commitment to direct patient care (OR 2.50, 95% CI 1.53-4.07). Personally rewarding hours per day were most strongly associated with career satisfaction (OR 5.28, 95% CI 2.72-10.2), life satisfaction (OR 4.46, 95% CI 2.34-8.48), and commitment to clinical practice (OR 3.46, 95% CI 1.87-6.39). Long-term relationships with patients were positively associated with career and life satisfaction and high life meaning. Burnout was strongly negatively associated with all measures of physician wellbeing. CONCLUSIONS: Intrinsic motivators (e.g., calling) were associated with each measure of physician well-being (satisfaction, meaning, and commitment), but extrinsic motivators (e.g., annual income) were not associated with meaning or commitment. Understanding the effects of intrinsic motivators may help inform efforts to support physician well-being.