Purpose: Prostate high-dose-rate brachytherapy (HDR-BT) planning involves determining the movement that a high-strength radiation stepping source travels through the patient's body, such that the resulting radiation dose distribution sufficiently covers tumor volumes and safely spares nearby healthy organs from radiation risks. The Multi-Objective Real-Valued Gene-pool Optimal Mixing Evolutionary Algorithm (MO-RV-GOMEA) has been shown to be able to effectively handle this inherent bi-objective nature of HDR-BT planning. However, in clinical practice there is a very restricted planning time budget (often less than 1 h) for HDR-BT planning, and a considerable amount of running time needs to be spent before MO-RV-GOMEA finds a good trade-off front of treatment plans (about20–30 min on a single CPU core) with sufficiently accurate dose calculations, limiting the applicability of the approach in the clinic. To address this limitation, we propose an efficiency enhancement technique for MO-RV-GOMEA solving the bi-objective prostate HDR-BT planning problem. Methods: Dose-Volume (DV) indices are often used to assess the quality of HDR-BT plans. The accuracy of these indices depends on the number of dose calculation points at which radiation doses are computed. These are randomly uniformly sampled inside target volumes and organs at risk. In available HDR-BT planning optimization algorithms, the number of dose calculation points is fixed. The more points are used, the better the accuracy of the obtained results will be, but also the longer the algorithms need to be run. In this work, we introduce a so-called multi-resolution scheme that gradually increases the number of dose calculation points during the optimization run such that the running time can be substantially reduced without compromising on the accuracy of the obtained results. Results and conclusion: Experiments on a data set of 18 patient cases show that with the multi-resolution scheme, MO-RV-GOMEA can achieve a sufficiently good trade-off front of treatment plans after five minutes of running time on a single CPU core (4–6 times faster than the old approach with a fixed number of dose calculation points). When the optimization with the multi-resolution scheme is run on a quad-core machine, five minutes are enough to obtain trade-off fronts that are nearly as good as those obtained by running optimization with the old approach in one hour (i.e., 12 times faster). This leaves ample time to perform the selection of the preferred treatment plan from the trade-off front for the specific patient at hand. Furthermore, comparisons with real clinical treatment plans, which were manually made by experienced BT planners within 30–60 min, confirm that the plans obtained by our approach are superior in terms of DV indices. These results indicate that our proposed approach has the potential to be employed in clinical practice.