The objective of this study was to evaluate the impact of intraprostatic calcifications (IC) on long-term tumor control in patients treated with permanent implant prostate brachytherapy (PIPB).Data from 609 I-125 patients treated with PIPB were retrospectively reviewed. The presence of IC was determined by reviewing postimplant CT images. Doses delivered were determined using the Monte Carlo (model-based) calculations and the TG43 approach. Biochemical relapses at 7 and 10 years were determined according to Phoenix definition. Long-term biochemical relapse-free survival (bRFS) was determined using Kaplan-Meier estimates with log rank test. Cox proportional hazard models were used for analysis of predictor factors of biochemical recurrence.IC were observed for 11.1% of patients. Clinical stage, PSA, Gleason score, D'Amico risk group, and ADT use were comparable between IC and no IC groups. The 7- and 10-year bRFS for the entire cohort were 94.1% and 90.6%, respectively. The bRFS at 7 years was 90.5% (with IC) vs. 94.5% (without IC) (p = 0.198); the corresponding values at 10 years were 78.8% vs. 91.8% (p = 0.046). On Cox model, only prostatic calcifications were a significant risk factor for biochemical relapse (HR: 2.30, IC 95%: 1.05-5.00, p = 0.037; and HR: 3.94; IC 95%: 1.00-15.38; p = 0.049 for univariate and multivariate analysis, respectively).The presence of IC in patients treated with PIPB decreases V and D for postimplant Monte Carlo dosimetry (compared with TG43); correspondingly, IC are associated with a lower 10-y bRFS. Model-based dose calculations are critical to evaluate potential cold spots due to calcifications.