PURPOSE: We aim to do an efficacy-safety analysis of Mirabegron-Tamsulosin combination therapy versus tamsulosin-placebo monotherapy in a select subset of medication virgin BPH patients with coexisting predominantly overactive bladder symptoms (OABS). METHODS: After prior written informed consent and institutional ethics clearance, 80 patients of uncomplicated BPH with coexisting OABS and IPSS of >7 were computer randomized and allocated to receive therapy with either [50mg Mirabegronplus Tamsulosin 0.4 mg (Intervention arm)]or [Tamsulosin 0.4 mg plus capsule lactobacillus (Comparator arm)] once daily for a period of 8 weeks. Efficacy was evaluated using the OABS Score (OABSS), mean change in the frequency of nocturnal voiding, post void residue (PVR) and international prostate symptom score (IPSS) while safety was assessed by recording treatment emergent adverse events (TEAE). The protocol was registered prospectively with the clinical trials registry of India (CTRI/2018/12/016541). RESULTS: Significant improvements were visualised in the primary endpoint total OABS subscore (OABSS-ss) at the end of 8 weeks in the combination group (mean difference -5.62 vs -2.22p< 0.001).Similar significant improvements were seen with most of the secondary parameters such as the mean change in voiding episode/night, IPSS, IPSS-ss,OABS-ss, voided volume/micturition, Qmax, and Quality of Life (QOL) indices (p<0.001). No significant increase in PVR was observed in the Mirabegron arm and no patient developed urinary retention. The TEAE were minor, self-limiting and were managed symptomatically without any treatment discontinuity. CONCLUSION: Mirabegron was significantly efficacious and safe in ameliorating OABS induced by BPH versus placebo. This efficacy can be safely enhanced by initiating Mirabegron-Tamsulosin combination therapy from the start in medication virgin patients as opposed to the usual add on therapy protocol. This combination appeared to be superior in terms of overall safety, minimal side effects, better compliance and tolerability versus Tamsulosin monotherapy particularly in the select subset of patients of with BPH coexisting/predominant OABS.