Objectives We aimed to investigate the effects of PCSK9 inhibitor on blood lipid levels in patients with high and very-high cardiovascular risk. Design 14 trials (n=52,586 patients) comparing treatment with or without PCSK9 inhibitors were retrieved from PubMed and Embase updated to 1st Jun 2021. The data quality of included studies was assessed by two independent researchers using the Cochrane systematic review method. All-cause mortality, cardiovascular mortality and changes in serum LDL-C, TC, TG, ApoB, LP (a), Non HDL-C, HDL-C and ApoA1 from baseline were analyzed using Rev Man 5.1.0 software. Results Compared to treatments without PCSK9 inhibitor, addition of PCSK9 inhibitors (evolocumab and alirocumab) had obvious decreasing effects on the levels of LDL-C [MD=-46.86, 95% CI (-54.99 to -38.72), P<0.00001], TC [MD=-31.92, 95% CI (-39.47 to -24.38), P<0.00001], TG [MD=-8.13, 95% CI (-10.48 to -5.79), P<0.00001], LP(a) [MD=-26.69, 95% CI (-27.93 to -25.44), P<0.00001], Non HDL-C [MD=-42.86, 95% CI (-45.81 to -39.92), P<0.00001] and ApoB [MD=-38.44, 95% CI (-42.23 to -34.65), P<0.00001] in high CVD risk patients. Conversely, changes of HDL-C [MD = 6.27, CI (5.17 to 7.36), P < 0.00001] and ApoA1 [MD = 4.33, 95% CI (3.53 to 5.13), P < 0.00001] from baseline were significantly more in high CVD risk patients who received PCSK9 inhibitors treatment. Conclusion Addition of PCSK9 inhibitors to standard therapy resulted in definite improvement in blood lipid levels than those therapies without its addition.