Background: DRE (digital rectal examination) suspicious for prostate cancer is still used as a clinical tool to diagnose prostate cancer. We aim to analyse the predictive value of DRE to diagnose prostate cancer ISUP grade group ≥2 (GG≥2) prostate cancer including the setting of STHLM3 test as a variable. Methods: The previously described STHLM3 screening-cohort included men between 50 to 70 years with ≥10% risk of prostate cancer as assessed by PSA or the Stockholm3 test and invited for transrectal biopsy (TRUSbx). All 7415 biopsied men was included for analysis. DRE status was categorized as T1-T4. We analysed sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) for DRE status of T2-4 to predict GG≥2 and GG≥3 in biopsies. In a multivariate logistic regression analysis; we adjusted for PSA, age, PVol, earlier biopsy (EB) and adjusted STHLM3 model risk set to exclude DRE and prostate volume (PVol). We calculated adjusted odds ratio (OR) for different strata of adjusted STHLM3 risk. Results: Prevalence of ISUP≥2 was 16.8% (1,243/7415). 9.7% (716/7415) men had DRE suspicious for cancer (T2-4) with a Sn to detect GG≥2 of 25.2%. Sp, PPV and NPV was 93.5%, 43.7% and 86.1%, respectively. In univariate model the OR for DRE T2-4 vs. T1 to predict GG≥2 was 4.28 (95% CI 4.09–5.67). Logistic regression analysis including also age, PVol, PSA, earlier biopsies and adjusted STHLM3 risk (%) gave an OR for DRE T2-4 of 2.87 (95% CI 2.36–3.49). In the same analysis stratified PSA group 5-10 ng/ml with PSA < 3 ng/ml as baseline gave OR = 3.21. Using the same univariate model, OR for DRE T2-4 vs. T1 to predict GG≥3 was 6.68 (95% CI 5.44–8.21) and in the multivariate model OR was 3.25 (95% CI 2.54–4.17). Conclusions: As a diagnostic test DRE holds little merit on its own but in combination with other clinical factors and biomarkers in this study we could show that it contributes with value. Just under half of men with DRE suspicious for cancer has GG≥2 cancer. This study does not establish evidence to rule out DRE as a clinically valuable adjunct to PSA, other clinical parameters and new biomarkers like STHLM3.