Background Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) often coexist and are associated with a high morbidity and reduced quality of life (QoL). Although these diseases share similarities in symptoms and clinical course, and exacerbations of both diseases often overlap, care pathways for both conditions are usually not integrated. This results in frequent outpatient consultations and suboptimal treatment during exacerbations, leading to frequent hospital admissions. Therefore, we propose an integrated care pathway for both diseases, using telemonitoring to detect deterioration at an early stage and a single case manager for both diseases. Objective This study aims to investigate whether an integrated care pathway using telemonitoring in patients with combined CHF and COPD results in a higher general health-related QoL (HRQoL) as compared with the traditional care pathways. Secondary end points include disease-specific HRQoL, level of self-management, patient satisfaction, compliance to the program, and cost-effectiveness. Methods This is a monocenter, prospective study using a quasi-experimental interrupted time series design. Thirty patients with combined CHF and COPD are included. The study period of 2.5 years per patient is divided into a preintervention phase (6 months) and a postintervention phase (2 years) in which end points are assessed. The intervention consists of an on-demand treatment strategy based on monitoring symptoms related to CHF/COPD and vital parameters (weight, blood pressure, heart rate, oxygen saturation, temperature), which are uploaded on a digital platform. The monitoring frequency and the limit values of the measurements to detect abnormalities are determined individually. Monitoring is performed by a case manager, who has the opportunity for a daily multidisciplinary meeting with both the cardiologist and the pulmonologist. Routine appointments at the outpatient clinic are cancelled and replaced by telemonitoring-guided treatment. Results Following ethical approval of the study protocol, the first patient was included in May 2018. Inclusion is expected to be complete in May 2021. Conclusions This study is the first to evaluate the effects of a novel integrated care pathway using telemonitoring for patients with combined CHF and COPD. Unique to this study is the concept of remote on-demand disease management by a single case manager for both diseases, combined with multidisciplinary meetings. Moreover, modern telemonitoring technology is used instead of, rather than as an addition to, regular care. Trial Registration Netherlands Trial Register NL6741; https://www.trialregister.nl/trial/6741 International Registered Report Identifier (IRRID) DERR1-10.2196/20571