A previous meta-analysis reported that: (i) an acute bout of prolonged uninterrupted sitting induces a significant increase in peripheral blood pressure (BP) and (ii) the increase in BP can be offset by interrupting the sitting bout with light aerobic activities such as walking. However, the temporal association between prolonged uninterrupted sitting and BP was not determined. A better understanding of temporality, for example, how long it takes BP to increase, will assist in prescribing sitting interruption strategies. We aimed to determine: (1) the temporal association between the duration of uninterrupted sitting and BP and (2) whether regular sitting interruptions moderate the association between uninterrupted sitting and BP. Electronic databases (PubMed, Web of Science, SPORTDiscus) were searched from inception to July 2022. Reference lists of eligible studies and relevant reviews were also screened. Inclusion criteria for objective (1) were: (i) participants aged ≥ 18years; (ii) a prolonged sitting bout ≥ 1h; and (iii) peripheral BP measurements (systolic BP, diastolic BP, and/or mean arterial pressure) at more than two timepoints during the sitting bout. Additional criteria for objective (2) were: (i) the sitting interruption strategy was implemented during the sitting bout (i.e., not prior to engaging in sitting) and (ii) the study included a control (uninterrupted sitting) condition or group. There were 1555 articles identified, of which 33 met inclusion criteria for objective (1). Of those articles, 20 met inclusion criteria for objective (2). To investigate the effect of sitting duration on the BP response, unstandardized b coefficients (mmHg/h) and 95% confidence intervals (CIs) were calculated using a three-level mixed-effect meta-regression. Increased sitting duration was positively associated with systolic BP (b = 0.42mmHg/h, 95% CI 0.18-0.60), diastolic BP (b = 0.24mmHg/h, 95% CI 0.06-0.42), and mean arterial pressure (b = 0.66mmHg/h, 95% CI 0.36-0.90). In trials where sitting was interrupted, there was a significant decrease in systolic BP (b = - 0.24mmHg/h, 95% CI - 0.42 to - 0.06) and diastolic BP (b = - 0.24mmHg/h, 95% CI - 0.42 to - 0.12), and a non-significant change in mean arterial pressure (p = 0.69). Increased uninterrupted sitting duration results in greater increases in BP; however, regularly interrupting sitting may offset negative effects.