Transurethral resection of the prostate (TUR-P) and transurethral resection of bladder tumor (TUR-BT) are common urological operations. Our aim was to show whether there was an association of the adenosine molecular pathway with postoperative pain level and malignancy status. A total of 93 patients with ages between 55 and 72 years old who underwent TUR-P (n = 47) and TUR-BT (n = 46) under spinal anesthesia between August 2017 and July 2018 were retrospectively analyzed. On the day of surgery, at the postoperative 24th and 48th hours, plasma adenosine levels and serum adenosine deaminase (ADA) levels were measured. The malignant group had significantly higher adenosine (median 171.51 IQR = 147.69-196.32 vs. median 57.82, IQR = 54.06-62.34, p < 0.001) and ADA levels (median 19.10, IQR = 12.85-22.05 vs. median 7.00, IQR = 5.80-10.80, p < 0.001) preoperatively. Although their levels decreased at the postoperative 24th and 48th hours, the levels remained significantly higher in the malignant group until the postoperative 24th hour (p < 0.001). Lower pain level during the first 36 h and less analgesic requirement during the first 24 h were observed in the malignant group (p < 0.001). In addition, patients with higher tumor grades experienced less pain up to the postoperative 6th hour (p < 0.016). A strong positive correlation was observed between adenosine and ADA levels before surgeries for all patients (rho = 0.637, p < 0.001). There were also negative correlations between VAS score and adenosine level (rho = - 0.721, p < 0.001) or VAS and ADA (rho = - 0.658, p < 0.001). In multivariate analysis, preoperative adenosine level (OR = 4.742, p < 0.001) was found to be the most important parameter affecting postoperative non-opioid analgesic requirement. According to our preliminary results, lower postoperative pain scores and less additional analgesic requirement may be associated with an increase in endogenous adenosine levels in malignant cases.