Recent empirical studies have shown that personality factors are associated with health care use (HCU). However, to date, a systematic review is lacking summarizing evidence regarding the link between personality factors and health care use or costs (i.e., monetarily valued health care use). Therefore, the objective of this systematic review is to provide an overview of evidence from observational studies investigating the link between personality characteristics and health care use or costs. Electronic databases (PubMed, PsycINFO, NHS EED) will be searched using predefined search terms. In an additional step, the reference lists of included studies will be searched (manually). No restrictions will be applied regarding the time of publication. Observational studies (both cross-sectional and longitudinal) assessing the link between personality characteristics and health care use/costs across all age categories will be included. Only studies using validated tools to quantify personality characteristics will be included. Among others, studies only focusing on mental HCU or studies only analyzing samples with a specific disorder (e.g., individuals with personality disorders) will be excluded. Mainly, data on methods (study design, measures, and statistical analysis), sample characteristics, and results regarding the link between personality and HCU/costs will be extracted. A quality assessment will be conducted. Two reviewers will perform the study selection, data extraction, and assessment of the study quality. If disagreements occur, they will be resolved through discussion to reach a consensus or by inclusion of a third party. Results will be presented narratively (text and tables). Depending on the number and heterogeneity of the studies included, a meta-analysis will be conducted. Results will be disseminated through publication in a peer-reviewed, scientific journal.