Each year approximately 1 million total hip replacements are performed worldwide. The most common indications to choose this procedure are rest pain and pain after activity as well as functional limitations influencing daily activities. Experimental pain is highly variable by individuals, which is partly due to genetics. The aim of the study was to investigate a possible association of the catechol-O-methyltransferase (COMT) and μ-opioid receptor (OPRM1) genotypes with pain perception in patients undergoing total hip replacement and total knee replacement taking into account aspects such as age, sex and diabetes. The study included 207 patients (119 females, 88 males, median age 65 years, range 33–77) that qualified for surgical treatment (total hip replacement and knee arthroplasty) due to osteoarthritis. Pain sensitivity measurement was performed using a standard algometer. The genomic DNA was extracted from the buccal cells.. Single locus analysis was conducted using a general linear model. In the study group, we did not find statistically significant genetic associations between variants of COMT and OPRM1 and pain thresholds/pain tolerance. The analysis of subjective pain perception using the visual analog scale did not show any relationship between the OPRM1 rs1799971A>G variant and COMT rs4680, rs4633, rs4818 and rs6269.