Objective: Feeling comfortable and safe has been discussed to foster health and well-being. However, the pathways to better health are complex, involving both behavioral and physiological routes. Methods: In this study, we examined the role of safety perception for cardiac health by (1) examining associations with baseline heart rate variability (HRV; Study 1) and (2) evaluating a novel measure of autonomic cardiac flexibility in daily life, namely increases in HRV independent of metabolic demands (ImdHRVi; Study 2). Results: Study 1 (N = 76) found evidence for a positive association between vagally mediated HRV and the Neuroception of Psychological Safety scale (Morton L, Cogan N, Kolacz J, et al. “A new measure of feeling safe: developing psychometric properties of the Neuroception of Psychological Safety Scale (NPSS)”: Correction.Psychol Trauma. 2022; https://doi.org/10.1037/tra0001374), thus suggesting a link between safety and cardiac vagal regulation. In Study 2, a sample of N = 245 adult volunteers participated in a four-day-ambulatory assessment measuring HRV and bodily movement. A regression was calculated between HRV and bodily movement for 12 h of the first recording day, which was then used to calculate minute-by-minute ImdHRVi (beyond those predicted by bodily movement) in the following days. It turned out that safety perception predicted more episodes of ImdHRVi in everyday life, even after controlling for several confounds. Conclusions: Findings suggest that feeling safe and everyday life cardiac autonomic regulation are interrelated, thus possibly contributing to adaptive adjustment and health.