Background: Recent studies on the PRESERFLO MicroShunt suggest that it may be effective in lowering intraocular pressure (IOP); however, the number of studies on this device remains limited. Therefore, we assessed the efficacy of the PRESERFLO MicroShunt in patients with glaucoma and performed a meta-analysis of published results. Methods: Prospective study including all patients that underwent PRESERFLO MicroShunt surgery from 2018 onwards. Sub-analyses were performed for cataract-combined procedures. To compare our results, we performed a systematic review and meta-analysis. IOP, IOP-lowering medication and surgical complications reported in the retrieved studies were assessed. Results: A total of 72 eyes underwent PRESERFLO-implant surgery (59 as standalone procedure and 13 as cataract-combined procedure). No significant differences were found in IOP and IOP-lowering medication between both groups. The mean ± standard deviation IOP and IOP-lowering medications of both groups taken together declined from 21.72 ± 8.35 to 15.92 ± 8.54 mmHg (p < 0.001, 26.7% reduction) and 3.40 to 0.93 (p < 0.001, 72.6% reduction) at 1 year follow-up, respectively. Secondary surgeries were required in 19.4% of eyes, the majority (71.4%) within 6 months. The meta-analysis including 14 studies (totaling 1213 PRESERFLO MicroShunt surgeries) from the systematic review showed a mean preoperative IOP and IOP-lowering medication of 22.28 ± 5.38 and 2.97 ± 1.07, respectively. The three-years postoperative pooled mean was (weighted mean difference, 95% CI) 11.07 (10.27 [8.23–12.32], p < 0.001) mmHg and 0.91 (1.77 [1.26–2.28], p < 0.001) for IOP and IOP-lowering medication, respectively. The most common reported complication was hypotony (2–39%). Conclusion: The PRESERFLO MicroShunt is effective and safe in lowering IOP and the number of IOP-lowering medications.