AIM: To compare the effectiveness and safety between modified cross-linking (MC) and standard cross-linking (SC) in mild or moderate progressive keratoconus. METHODS: Eligible studies were retrieved from four electronic databases, including CENTRAL, Clinical Trials gov, PupMed and OVID MEDLINE. We set post-surgical maximum K value (Kmax) as the primary outcome. In addition, uncorrected and corrected distant visual acuity (UDVA and UDVA), spherical equivalent (SE), endothelial cell density (ECD), central cornea thickness (CCT) and depth of demarcation line (DDL) were Meta-analyzed as secondary outcomes. Mean differences for these outcomes were pooled through either a random-effect model or fixed-effect model according to data heterogeneity. RESULTS: Twenty-four comparative studies either on accelerated cross-linking (AC) compared with SC or on trans-epithelial cross-linking (TC) compared with SC were included and pooled for analysis. The results indicated that MC was significantly inferior to SC at delaying Kmax deterioration [AC vs SC 0.49 (95% CI: 0.04-0.94, I2=75%, P=0.03); TC vs SC 1.15 (95% CI: 0.54-1.75, I2=50%, P=0.0002)]. SE decreased significantly for SC when compared to AC [0.62 (95% CI: 0.38-0.86, I2=22%, P<0.00001)]. DDL of SC was more significantly deeper than that of TC [-133.49 (95% CI: -145.94 to -121.04, I2=33%, P<0.00001)]. Other outcomes demonstrated comparable results between MC and SC. CONCLUSION: SC is more favorable at halting the progression of keratoconus, but visual acuity improvement showed comparable results between MCs and SC.