Abstract Background Due to a number of methodological advantages and theoretical considerations, more and more studies in clinical psychology research employ the Experience Sampling Method (ESM) as a data collection technique. Despite this growing interest, the absence of methodological guidelines related to the use of ESM has resulted in a large heterogeneity of designs while the potential effects of the design itself on the response behavior of the participants remain unknown. The objectives of this systematic review are to investigate the associations between the design characteristics and the data quality and feasibility of studies relying on ESM in severe psychiatric disorders. Methods We will search for all published studies using ambulatory assessment with patients suffering from major depressive disorder, bipolar disorder, and psychotic disorder or individuals at high risk for these disorders. Electronic database searches will be performed in PubMed and Web of Science with no restriction on the publication date. Two reviewers will independently screen original studies in a title/abstract phase and a full-text phase based on the inclusion criteria. The information related to the design and sample characteristics, data quality, and feasibility will be extracted. We will provide results in terms of a descriptive synthesis, and when applicable, a meta-analysis of the findings will be conducted. Discussion Our results will attempt to highlight how the feasibility and data quality of ambulatory assessment might be related to the methodological characteristics of the study designs in severe psychiatric disorders. We will discuss these associations in different subsamples if sufficient data are available and will examine limitations in the reporting of the methods of ambulatory studies in the current literature. Systematic review registration The protocol for this systematic review was registered on PROSPERO (PROSPERO 2017: CRD42017060322 ) and is available in full on the University of York website ( http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017060322 ).