Background: Data from the Middle East regarding second primary malignancy (SPM) after radical prostatectomy are limited. Our objective was to estimate the overall risk of developing second primary malignancy (SPM) among Middle Eastern men with prostate cancer who underwent surgical extirpation of their prostate. Materials and methods: We conducted a retrospective study of 406 patients who underwent radical prostatectomy in a tertiary centre and who had no evidence of previous malignancy from 1998 to 2012. Standardized incidence ratios (SIRs) and 95% confidence interval (CI) were calculated to analyze the risk of SPM in our population compared with the general population. Cox-regression models were also conducted to correlate the clinicopathological factors with the development of SPM. Results: After 14 years of follow-up, the incidence rate of SPM was 100.9 per 1,000 person-years. The most frequent SPMs were bladder cancer (n = 11, 27%) followed by hematological malignancies (n = 9, 22%) and lung cancer (n = 7, 17%). The overall risk for men with prostate cancer to develop SPM is lower than the men in the general population (standardized incidence ratios = 0.19; 95% CI: 0.14–0.25). A multivariate analysis failed to correlate any of the clinicopathological factors with the development of SPM. Conclusion: Patients with prostate cancer who underwent surgical expiration of their prostate are at lower risk of developing SPM compared with the general population. Keywords: Prostate Cancer, Radical Prostatectomy, Second Primary Malignancies, Standardized Incidence Ratio