Compromised well-being in health care workers (HCWs) is detrimental to the workforce, organizations, and patients. To test the effectiveness of Well-Being Essentials for Learning Life-Balance (WELL-B), a web-based continuing education program to deliver brief, evidence-based, reflective, psychological interventions to improve 4 dimensions of HCW well-being (ie, emotional exhaustion, emotional thriving, emotional recovery, and work-life integration). A randomized clinical trial (RCT) of US inpatient and outpatient HCWs randomized 1:1 was conducted from January 3 through May 31, 2023, using a web-based intervention. Cohort 1 received 5 hours of WELL-B over 8 days; cohort 2 acted as the control group and received WELL-B after the end of the RCT. Eligibility criteria were US HCWs aged 18 years or older, including clinical (physician, nurse, and respiratory therapist) and nonclinical (administrative, information technology, and finance) roles. Continuing education sessions exposed participants to positive psychology interventions (gratitude letter, work-life integration, self-compassion and cultivating awe). The primary outcome was emotional exhaustion on day 8; secondary outcomes included emotional thriving, emotional recovery, and work-life integration. All outcomes were measured using psychometrically valid scales previously reported in well-being RCTs and were assessed on days 1 and 8 (primary end point). Differences in outcome measures between the WELL-B intervention group and controls were assessed using t tests. Baseline-adjusted multiple linear regression models were evaluated to examine the association between the WELL-B intervention and the outcome measures after adjusting for additional covariates (sex, race and ethnicity, age, HCW role, and discipline). Intention-to-treat analysis was performed. The cohorts were similar at baseline, mostly female (528 [89%]) and nurses (177 [30%]). A total of 643 respondents participated in the study. In cohort 1, 331 participants initiated WELL-B, and 262 (71%) completed the day 8 follow-up; in cohort 2, 312 participants initiated WELL-B and 291 (77%) completed the day 8 follow-up. Compared with the control cohort, WELL-B significantly improved emotional exhaustion (estimate: -9.0; 95% CI, -13.1 to -4.9; P < .001), emotional thriving (estimate: 6.6; 95% CI, 3.2-10.0; P < .001), emotional recovery (estimate: 5.5; 95% CI, 2.0-9.0; P = .002), and work-life integration (estimate: -5.0; 95% CI, -8.2 to -1.9; P = .002). After adjusting for baseline outcome measures, sex, race and ethnicity, age, HCW role, and discipline, the linear regression model showed WELL-B improved day 8 emotional exhaustion (estimate: -9.6; 95% CI, -12.5 to -6.6; P < .001) compared with the control group. Favorable impressions of WELL-B were reported by more than 90% of the participants. In this RCT, brief well-being activities delivered during continuing education sessions improved short-term HCW emotional exhaustion, emotional thriving, emotional recovery, and work-life integration, with and without adjusting for covariates. Health care worker impressions of WELL-B were positive. These findings suggest that WELL-B is a beneficial intervention. ClinicalTrials.gov Identifier: NCT05636072.