Background: Physical activity positively influences cardiovascular health. Results from male-dominated physically active occupations suggest that a high level of occupational physical activity may be detrimental to cardiovascular health. This observation is referred to as the physical activity paradox. Whether this phenomenon can also be observed in female-dominated occupations remains unknown. Objective: We aimed to provide an overview of (1) leisure-time and occupational physical activity in healthcare workers. Therefore, we reviewed studies (2) to assess the relationship between the two physical activity domains and analyzed (3) their effects on cardiovascular health outcomes in relation to the paradox. Methods: Five databases (CINAHAL, PubMed, Scopus, Sportdiscus, Web of Science) were systematically searched. Both authors independently screened the titles, abstracts, and full texts and assessed the quality of the studies using the National Institutes of Health's quality assessment tool for observational cohort and cross-sectional studies. All studies that assessed leisure-time and occupational physical activity in healthcare workers were included. The two authors independently rated the risk of bias using the ROBINS-E tool. The body of evidence was evaluated using the GRADE approach. Results: The review included 17 studies that assessed the leisure-time and occupational physical activity of people working in healthcare, determined the relationship between the domains (n = 7) and/or examined their effects on the cardiovascular system (n = 5). Measurements for leisure-time and occupational physical activity varied between studies. Leisure-time physical activity typically ranged between low and high intensity, with a short duration (approx. 0.8–1.5 h). Occupational physical activity was typically performed at light to moderate intensity with a very long duration (approx. 0.5–3 h). Moreover, leisure-time and occupational physical activity were almost negatively related. The few studies investigating effects on cardiovascular parameters revealed a rather unfavorable effect of occupational physical activity, while leisure-time physical activity was beneficial. The study quality was rated as fair and the risk of bias was moderate to high. The body of evidence was low. Conclusions: This review confirmed that leisure-time and occupational physical activity of healthcare workers are opposed in their duration and intensity. Moreover, leisure-time and occupational physical activity seem to be negatively related and should be analyzed according to their relation to each other in specific occupations. Furthermore, results support the relationship between the paradox and cardiovascular parameters. Registration: Preregistered on PROSPERO (CRD42021254572). Date of registration on PROSPERO: 19 May 2021. Tweetable abstract: Does occupational physical activity adversely affect the cardiovascular health of healthcare workers in comparison to leisure-time physical activity?