The combination of systematic and targeted biopsy in Magnetic Resonance Imaging (MRI)/ Ultrasound (US) fusion technique improves the diagnosis of clinically significant prostate cancer. Using in-bore MR-guided prostate biopsy (IBMRGpB), which is considered to be the most accurate MR-guided sampling technique, many practitioners omit systematic biopsy. We sought to quantify the additive value of systematic biopsy (SB) using in-bore magnetic resonance (MR)-guided prostate biopsy (IBMRGpB). We retrospectively reviewed the records of 189 patients who underwent IBMRGpB in Sheba Medical Center between 2017-2022. SB;was performed in all patients. Endpoints included clinically significant and non-clinically significant cancer diagnoses. A subgroup analysis for 73 biopsy naïve patients was performed. We used Chi-square, T-test, and Mann-Whitney for statistical analysis. Logistic regression was used to find indicators for clinically significant disease on systematic biopsy. Statistical analysis was performed using SPSS Version 22 (IBM corps). Median age was 68y (IQR 62-71.5), mean PSA was 8.7±8.2 ng/dL.;The median number of cores per biopsy was 17 (IQR 16-19) of which 5 (IQR 4-7) were targeted.;SB detected clinically significant disease in 67 (35.5%) patients. Five (2.65%) patients whose targeted biopsies found benign or non-clinically significant disease had clinically significant disease on SB. SB from the lobe contralateral to the lesion detected clinically significant disease in 15 (12%) patients. The size of the prostate was larger, and the percentage of lesions located in the peripheral zone of the prostate was higher in patients with SB-detected clinically significant disease. The location of the main lesion in the peripheral zone of the prostate was a predictor for clinically significant disease on SB in multivariate analysis (OR=8.26, p=0.04), a finding supported by a subgroup analysis of biopsy-naïve patients (OR=10.52, p=0.034). The addition of SB during IBMRGpB increased the diagnosis of clinically significant as well as non-clinically significant prostate cancer. The location of the main lesion in the peripheral zone emerged as a positive predictive factor for clinically significant disease on SB. These findings may enhance patient-tailored management. [ABSTRACT FROM AUTHOR]