Objective: The purpose of this study was to retrospectively assess the efficacy and safety of minimally invasive nephrolithotomy (MPCNL) versus retrograde intrarenal surgery (AIRS) in the management of upper urinary stones. Methods: A comprehensive literature review of articles that investigated the efficacy and safety of MPCNL and AIRS was conducted by systematically searching PubMed, EMBASE, and Cochrane Library in March 2019. Two reviewers searched the literature, independently extracted the data and evaluated the quality of the data according to the inclusion and exclusion criteria. A meta-analysis was performed by using Review Manager 5.3 software. Results: Eight randomized controlled trials (RCTs) involving 725 patients with upper urinary stones were analysed based on the inclusion criteria. While MPCNL has a better clinical efficacy than AIRS with respect to the stone-free rate (SFR) [RR = 1.11, 95% CI (1.05-1.17), p = 0.0005], MPCNL has a higher incidence of haematoma [RR = 3.09, 95% CI (1.44-6.66), p = 0.004] and longer hospitalization time [MD = 0.89 day, 95% CI (0.07-1.72), p = 0.04]. In addition, no significant difference in operative time [MD = 2.46 min, 95% CI ( -17.99 to 22.92), p = 0.81] and postoperative pain score [MD = 0.74, 95% CI ( - 0.45 to 1.94), p = 0.22] were observed between the two methods. Overall, the evidence was insufficient to suggest a statistically significant difference in the adverse event profile for MPCNL compared with AIRS. Conclusions: Our data suggest that MPCNL is an effective method for treating upper urinary stones, especially lower calyceal stones that are 1-2 cm in size. Compared to AIRS, MPCNL is associated with a longer hospital stay time and a higher incidence of haematoma. In addition, both methods have proven to be safe. Nevertheless, the findings should be further confirmed through well-designed prospective RCTs with a larger patient series.