<b><i>Objective:</i></b> To assess the safety and efficacy of ultrasonographic vs. fluoroscopic access for percutaneous nephrolithotomy (PCNL). <b><i>Methods:</i></b> Medline (PubMed), Embase, Ovid, Cochrane, and the Chinese Biomedical Literature databases were searched to identify clinically controlled trials (CCTs) and randomized controlled trials (RCTs) that compared ultrasonographic access with fluoroscopic access for PCNL. RevMan 5.1 software and Stat Manager V4.1 software were used for the meta-analysis. <b><i>Results:</i></b> Five RCTs and nine CCTs were included in our study, which contained a total of 3,019 patients. Of these, 1,574 (52%) had undergone ultrasonographic access, and 1,445 (48%) had undergone fluoroscopic access. The pooled results revealed that the ultrasonographic access patients had shorter duration of access (min) by 2.56 min (weighted mean difference (WMD) = −2.56, 95% confidence interval (CI): −4.40 to −0.72, p = 0.006). There was a higher stone-free rate in the ultrasonographic access group (odds ratio (OR) = 1.26, 95% CI: 1.02-1.55, p = 0.03), as well as a lower rate of operative complications (OR = 0.72, 95% CI: 0.56-0.93, p = 0.01), reduced intraoperative blood loss (ml) (WMD = −14.55 ml, 95% CI: −27.65 to −1.46, p = 0.03), and a lower rate of blood transfusion requirement (OR = 0.39, 95% CI: 0.24-0.63, p = 0.0001). Sensitivity and subgroup analyses were also performed. <b><i>Conclusion:</i></b> Except for no radiation exposure, our meta-analysis revealed that ultrasonographic access had many advantages, such as a shorter access time, reduced intraoperative blood loss, a lower rate of operative complications, a lower rate of blood transfusion, and a higher stone-free rate. Because of these significant advantages, we recommend the use of ultrasonographic access for PCNL
