Missed test results, defined as test results not followed up within an appropriate time frame, are common and lead to delays in diagnosis and treatment. To evaluate the effect of a quality improvement collaborative, the Virtual Breakthrough Series (VBTS), on the follow-up rate of 2 types of test results prone to being missed: chest imaging suspicious for lung cancer and laboratory findings suggestive of colorectal cancer. This stepped-wedge cluster-randomized clinical trial was conducted between February 2020 and March 2022 at 12 Department of Veterans Affairs (VA) medical centers, with a predefined 3-cohort roll-out. Each cohort was exposed to 3 phases: preintervention, action, and continuous improvement. Follow-up ranged from 0 to 12 months, depending on cohort. Teams at each site were led by a project leader and included diverse interdisciplinary representation, with a mix of clinical and technical experts, senior leaders, nursing champions, and other interdisciplinary team members. Analysis was conducted per protocol, and data were analyzed from April 2022 to March 2024. All teams participated in a VBTS, which included instruction on reducing rates of missed test results at their site. The primary outcome was changes in the percentage of abnormal test result follow-up, comparing the preintervention phase with the action phase. Secondary outcomes were effects across cohorts and the intervention's effect on sites with the highest and lowest preintervention follow-up rates. Previously validated electronic algorithms measured abnormal imaging and laboratory test result follow-up rates. A total of 11 teams completed the VBTS and implemented 47 (mean, 4 per team; range, 3-8 per team; mode, 3 per team) unique interventions to improve missed test results. A total of 40 027 colorectal cancer-related tests were performed, with 5130 abnormal results, of which 1286 results were flagged by the electronic trigger (e-trigger) algorithm as being missed. For lung cancer-related studies, 376 765 tests were performed, with 7314 abnormal results and 2436 flagged by the e-trigger as being missed. There was no significant difference in the percentage of abnormal test results followed up by study phase, consistent across all 3 cohorts. The estimated mean difference between the preintervention and action phases was -0.78 (95% CI, -6.88 to 5.31) percentage points for the colorectal e-trigger and 0.36 (95% CI, -5.19 to 5.9) percentage points for the lung e-trigger. However, there was a significant effect of the intervention by site, with the site with the lowest follow-up rate at baseline increasing its follow-up rate from 27.8% in the preintervention phase to 55.6% in the action phase. In this cluster-randomized clinical trial of the VBTS intervention, there was no improvement in the percentage of test results receiving follow-up. However, the VBTS may offer benefits for sites with low baseline performance. ClinicalTrials.gov Identifier: NCT04166240.