The study investigates the effectiveness and appropriateness of the Drug Abuse Resistance Education (D.A.R.E.) Keepin’ it REAL (KiR) curriculum – America’s most prevalent in-school prevention programme – using a modified systematic review procedure as adapted from the Cochrane Handbook. No published studies research the D.A.R.E. version of KiR, and so we consider the Keepin’ it REAL intervention as a whole. After reviewing the abstracts of 677 studies matching relevant keyword searches, 11 studies matched inclusion criteria (e.g. testing effectiveness on substance use). The systematic review yields mixed results for the effectiveness of the Keepin’ it REAL intervention. Concerns remain regarding the appropriateness of the KiR D.A.R.E. programme: (1) KiR has only been tested on a narrow audience and may not be appropriate for D.A.R.E.’s larger audience, (2) KiR may not be effective in reducing substance use among elementary school students and (3) the specific versions of KiR implemented by D.A.R.E. (KiR D.A.R.E. and KiR D.A.R.E. Elementary) have yet to be tested for efficacy. The authors recommend independent, randomised trials for the KiR D.A.R.E. curriculum and the development of a standardised measure and evaluation system for in-school substance use prevention programmes.