Objective To perform a systematic review and meta-analysis comparing overall prostate cancer detection rate and clinically-significant prostate cancer detection rate between MRI-ultrasound image guided fusion biopsy (MRI-US FB) and cognitive biopsy (CB). Methods A systematic review of Pubmed, EMBASE, MEDLINE, and Cochrane library databases was performed. Identified studies were assessed for clinical relevance and excluded based on a set of predefined criteria. Final articles included in the analysis comprised only prospective trials that compared CB vs. MRI-US FB in men with MRI-identifiable lesions (Prostate Imaging Reporting and Data System score 2+). Articles were reviewed for patient demographics, MRI protocol, and rates of overall and clinically significant prostate cancer detection by both modalities. Results Nine studies were analyzed. A composite 1,714 men with mean age 64.6 years and mean PSA 8.2 ng/dL were reviewed. When comparing FB to CB, the odds ratio for overall and for clinically significant prostate cancer detection was 1.11 (95%CI 0.91–1.36, P = 0.30) and 1.13 (95%CI 0.89–1.44, P = 0.32), respectively. Heterogeneity among the studies was moderate but not significant for either overall (X2 = 14.67; I2 = 45%; P = 0.07) or clinically significant prostate cancer detection (X2 = 11.81; I2 = 49%; P = 0.07). Conclusion MRI-US FB demonstrates a trend toward improved rates of prostate cancer detection compared to CB, although this is not statistically significant. Further comparative studies may help to further elucidate whether one of these modalities is superior over the other.