Objective: To synthesize contemporary evidence of the impact of contralateral prophylactic mastectomy (CPM) on survival outcomes in patients with unilateral breast cancer (UBC). Methods: PubMed, EMBASE and Scopus databases were searched for observational studies published up to November 15, 2023. Random-effects model was used to obtain pooled effect estimates that were reported as hazards ratio (HR) with 95% confidence intervals (CI). The outcomes of interest were overall survival (OS), breast cancer-specific survival (BCSS), recurrence free survival (RFS) and risk of contralateral breast cancer (CBC). Results: Twenty-one studies were included. Most studies had a retrospective design. CPM was associated with significant improvement of OS (HR 0.80, 95% CI: 0.75, 0.85), BCCS (HR 0.82, 95% CI: 0.74, 0.90), and RFS (HR 0.72, 95% CI: 0.60, 0.86) and significantly reduced risk of CBC (HR 0.05, 95% CI: 0.03, 0.09) in patients with UBC. No evidence of publication bias was detected. Conclusion: Our results provide strong evidence supporting the positive impact of CPM on survival outcomes in patients with UBC. Further research and long-term follow-up studies are warranted to validate these findings. doi: https://doi.org/10.12669/pjms.40.8.9708 How to cite this: Yao M, Peng P, Chen L, Xu Z. Impact of contralateral prophylactic mastectomy on survival outcomes in patients with unilateral breast cancer: A systematic review and meta-analysis. Pak J Med Sci. 2024;40(8):---------. doi: https://doi.org/10.12669/pjms.40.8.9708 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.