The present study aimed to assess current evidence on the effectiveness and safety of minimally invasive vs. standard percutaneous nephrolithotomy (PCNL) in the management of renal stones. A systematic search of electronic databases, which included PubMed, EMBASE and the Cochrane Library up to May 2019 was performed. Using Review Manager statistical software (version 5.3), primary outcomes, including stone-free rates (SFRs), were evaluated. Meanwhile, analysis was also performed to compare secondary outcomes, such as peri- and postoperative complications and operative data. Fourteen studies involving 1,611 patients with renal stones were analyzed based on the inclusion criteria. On the basis of the present analysis, mini percutaneous nephrolithotomy (MPCNL) was proven to have non-inferior clinical efficacy with respect to the SFR compared with PCNL [odds ratio (OR)=1.10; 95% confidence interval (CI), 0.84-1.44; P=0.48]. In addition, the meta-analysis showed that MPCNL had a significantly lower hemoglobin decrease [mean difference (MD)=-0.68; 95% CI, -1.05 to -0.31; P=0.0003] and fewer blood transfusions (OR=0.36; 95% CI, 0.18-0.71; P=0.003) compared with PCNL. Moreover, the MPCNL group had a shorter inpatient stay (MD=-0.81; 95% CI, -1.55 to -0.08; P=0.03) compared with the PCNL group. However, the overall evidence was insufficient to suggest a statistically significant difference in the adverse event profile for MPCNL compared with PCNL. The present meta-analysis indicates that MPCNL is an effective method for treating renal stones. Compared with PCNL, MPCNL not only has similarly high SFRs but is also associated with less blood loss, fewer blood transfusions, more favorable recovery time and shorter inpatient stays. However, the findings of the present study should be further confirmed by well-designed prospective randomized controlled trials with a larger patient series.