Background: The prevalence of hypertension is a major public health challenge. Despite it being highly preventable, hypertension is responsible for a significant proportion of global morbidity and mortality. Common methods for controlling hypertension include prescribing anti-hypertensive medication, a pharmacological approach, and increasing physical activity, a behavioural approach. In general, little is known about the comparative effectiveness of pharmacological and behavioural approaches for reducing blood pressure in hypertension. A previous network meta-analysis suggested that physical activity interventions may be just as effective as many anti-hypertensive medications in preventing mortality; however, this analysis did not provide the comparative effectiveness of these disparate modes of intervention on blood pressure reduction. The primary objective of this study is to use network meta-analysis to compare the relative effectiveness, for blood pressure reduction, of different approaches to increasing physical activity and different first-line anti-hypertensive therapies in people with hypertension.Methods: A systematic review will be conducted to identify studies involving randomised controlled trials which compare different types of physical activity interventions and first-line anti-hypertensive therapy interventions to each other or to other comparators (e.g. placebo, usual care) where blood pressure reduction is the primary outcome. We will search the Cochrane Library, MEDLINE and PsycInfo. For studies which meet our inclusion criteria, two reviewers will extract data independently and assess the quality of the literature using the Cochrane Risk of Bias Tool. Network meta-analyses will be conducted to generate estimates of comparative effectiveness of each intervention class and rankings of their effectiveness, in terms of reduction of both systolic and diastolic blood pressure.Discussion: This study will provide evidence regarding the comparability of two common first-line treatment options for people with hypertension. It will also describe the extent to which there is direct evidence regarding the comparative effectiveness of increasing physical activity and initiating anti-hypertensive therapy.