OBJECTIVE: To synthesize evidence on the effectiveness of consultation-based interventions on adherence to primary or secondary preventative medications and clinical outcomes. We focused on consultation-based interventions suitable for primary care settings, without needing specific technologies, and with reasonable time requirements of clinicians. METHODS: A database search was undertaken from 2015 onwards, supplemented by previous systematic reviews and citation-searching. Randomized trials targeting adults prescribed long-term medication for cardiovascular prevention, type 2 diabetes mellitus (T2DM), chronic respiratory disease, or osteoporosis were included. Interventions had to meet a priori eligibility criteria for implementation feasibility in primary care. Two reviewers screened, extracted data, and assessed risk of bias using the Cochrane RoB2 tool. Adherence and clinical outcomes were assessed, with meta-analyses conducted using inverse variance heterogeneity methods and sensitivity analyses to explore heterogeneity. RESULTS: 41 studies (n = 26 114) were included. Meta-analysis showed significant adherence improvements for T2DM [standardized mean difference (SMD) 0.60, 95% confidence interval (CI) 0.10 to 1.11] and chronic respiratory disease (SMD 0.22, 95% CI 0.07 to 0.38), but effects were not robust to sensitivity analyses. No significant adherence effects were observed for cardiovascular prevention nor osteoporosis. Interventions did not significantly improve clinical outcomes including systolic blood pressure, low-density lipoprotein, HbA1c (after sensitivity analyses), respiratory symptoms, or hospitalization. High heterogeneity and study-level risk of bias limited certainty. CONCLUSION: Consultation-based interventions may modestly improve medication adherence in T2DM and chronic respiratory disease, but there is no robust evidence of clinical benefit, nor evidence of effectiveness in other conditions. Intervention feasibility is an important consideration for guiding future research and translating it into practice.