Patients with chronic kidney disease (CKD) have altered physiologic processes, which result in different treatment outcomes compared with the general population. We aimed to systematically evaluate the efficacy of clinical interventions in reducing mortality of patients with CKD. We searched PubMed, MEDLINE, Embase, and Cochrane Database of Systematic Reviews for meta-analyses of randomized controlled trials (RCT) or observational studies (OS) studying the effect of treatment on all-cause mortality of patients with CKD. The credibility assessment was based on the random-effects summary estimate, heterogeneity, 95% prediction intervals, small study effects, excess significance, and credibility ceilings. Ninety-two articles yielded 130 unique meta-analyses. Convincing evidence from OSs supported mortality reduction with three treatments: angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers for patients not undergoing dialysis, warfarin for patients with atrial fibrillation not undergoing dialysis, and (at short-term) percutaneous coronary intervention compared to coronary artery bypass grafting for dialysis patients. Two treatment comparisons were supported by highly credible evidence from RCTs in terms of all-cause mortality. These were high-flux hemodialysis (HD) versus low-flux HD as a maintenance HD method and statin versus less statin or placebo for patients not undergoing dialysis. Most significant associations identified in OSs failed to be replicated in RCTs. Associations of high credibility from RCTs were in line with current guidelines. Given the heterogeneity of CKD, it seems hard to assume mortality reductions based on findings from OSs.