Background <p>Total prostate-specific antigen (tPSA) could be elevated in some cases of benign prostate enlargement (BPE). The aim of this study is to evaluate tPSA clearance after surgery for BPE with histologic confirmation of nodular hyperplasia.</p> Methods <p>Men for transurethral resection of the prostate (TURP), or open simple prostatectomy (OSP), with benign imaging features of the prostate were recruited. Those with tPSA &gt;4ng/ml, but benign core-needle biopsy reports were recruited as well. A control arm of men on Tamsulosin+Dutasteride therapy (TDT) for BPE was also recruited. Participants with histologic finding of chronic prostatitis or malignancy at biopsy or post extirpation were excluded. Age, body mass index (BMI), prostate volume (PV) and presenting clinical features were noted. The tPSA values were taken at baseline, 6 weeks and 12 weeks post intervention. The mass of resected or enucleated prostate tissue was noted and the tPSA clearance curve was plotted.</p> Results <p>There were 154 participants: 77 were on TDT, 43 had monopolar TURP and 34 had OSP. The TDT patients were younger (61.57 ± 6.93years TDT vs. 65.4 ± 9.08years TURP vs. 63.71 ± 7.23years OSP; p 0.03), had lower median tPSA [5.6(4.0–7.6)ng/ml TDT vs. 10.0(5.7–13.1)ng/ml TURP vs. 15.8(9.0–20.0)ng/ml OSP; <i>p</i> &lt; 0.001], and had lower PV (51.96 ± 5.22&#xa0;ml TDT vs. 62.42 ± 7.16&#xa0;ml TURP vs. 113.13 ± 29.57&#xa0;ml OSP; <i>p</i> &lt; 0.001) at recruitment. The 3 groups had similar BMI (26.25 ± 1.68&#xa0;kg/m² TDT vs. 25.72 ± 2.72&#xa0;kg/m² TURP vs. 26.05 ± 2.23&#xa0;kg/m² OSP; p 0.44). The tPSA clearance post-surgery correlated with the pre-surgery tPSA and was at a rate of y = 11.168e^− 0.151x (y=tPSA; x=time). At 6 weeks post-surgery, 45.5% had tPSA &lt; 4.0ng/ml, and at 12 weeks, 96.1% had tPSA &lt; 4.0ng/ml.</p> Conclusion <p>Where tPSA is ≥ 1.5ng/ml in BPE, surgery in form of TURP or OSP results in exponential decrease in serum tPSA.</p>