To assess the 12-month cost-effectiveness of the nurse-led transitional care program "Cardiolotse" (CL) for patients with cardiovascular diseases compared to usual care (UC). A cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) were conducted from the perspective of statutory health insurance (SHI), covering a time horizon of 12 months. Analyzed outcomes included the number of rehospitalizations and health-related quality of life (HRQoL). Total costs comprised program costs and the utilization of healthcare resources. Point estimates are presented as incremental cost-effectiveness ratios (ICERs) and incremental cost-utility ratios (ICURs). Sensitivity and subgroup analyses were conducted to illustrate uncertainty and provide insights into the impact mechanisms of the CL program. The study population consisted of 2550 patients, with 1256 allocated to the intervention group and 1294 to the control group. Patients who received support from CLs experienced fewer rehospitalizations and lower inpatient costs from an SHI perspective, compared to the UC group. HRQoL assessments indicated higher utility values for CL patients at the 12-month follow-up. Total program costs amounted to €1454.65 per patient. The CEA and CUA demonstrate that the CL program is dominant compared to UC from the SHI perspective. Our study shows that the CL program not only reduces the number of rehospitalizations and costs but increases HRQoL, resulting in a dominant ICER and ICUR. Further research is necessary to evaluate longer periods of time, different levels of care intensity, and perspectives of different healthcare stakeholders. German Clinical Trial Register DRKS00020424, 2020-06-18, retrospectively registered.