BACKGROUND: Amputation leads to significant physical, psychological, and emotional challenges, with chronic pain being among the most debilitating outcomes. Conditioned Pain Modulation (CPM) is a key mechanism for understanding pain modulation reflecting the central nervous system's capacity to regulate pain. OBJECTIVE: This study aimed to evaluate CPM in amputees, comparing CPM between the amputated and non-amputated sides, and to identify factors influencing CPM in this population. METHOD: Eighty-six amputees participated in the study. Sociodemographic and pain-related variables, including age, occupation, smoking status, pre-amputation pain duration, phantom limb pain, and pressure pain threshold, were assessed. Multiple linear regression models were performed to explore factors associated with CPM on both sides, with additional -tests to compare CPM values between sides. RESULTS: The multivariate model for the amputated side explained 26.3% of CPM variability, with significant associations found for pre-amputation pain duration and retirement status, as well as PPT mean of the amputated side, smoking, and phantom limb pain and age. In contrast, the non-amputated side model explained 26.5% (Adjusted R-squared) of the variability, with the following significant variables: duration of pre-amputation pain (negative correlation), smoking history, phantom limb pain (negative correlation), and frequency of telescoping sensation (negative correlation). There were no significant differences in CPM between amputated and non-amputated sides ( > 0.05). CONCLUSION: The findings suggest that CPM on the amputated side is more influenced by pain experience and sociodemographic variables, while the non-amputated side shows less variability and is more resilient to these influences.