Background: Pregabalin, approved for various medical conditions, has shown increasing misuse potential globally. However, limited research exists on pregabalin dependence in India. This study aimed to investigate the prevalence and characteristics of pregabalin dependence among individuals seeking substance use disorder (SUD) treatment in North India. Methods: A cross-sectional, analytical study was conducted on patients enrolled between August 2022 and July 2023 at an academic institution-based addiction treatment center. Case records of patients with pregabalin dependence were retrieved and compared with controls with opioid dependence but no history of pregabalin use. Results: Among 3766 registered patients, 135 had pregabalin dependence (prevalence: 3.58 per 100 registered patients). Pregabalin-dependent patients were male, with a median usage duration of eight months and a median daily dose of 1200 mg. Most had concurrent opioid dependence, primarily heroin, used via the injection route. The odds of pregabalin dependence among those with opioid dependence were significantly higher than those with other substance dependence (OR 1.44, 95% CI 1.13–1.85). Reasons for pregabalin use included opioid craving reduction, sedation, and euphoria. Patients with pregabalin dependence were more likely to have lower socioeconomic status (P < 0.0001) and urban residence (P = 0.032), an earlier age of substance use initiation (P = 0.02) and treatment seeking (P < 0.0001), and a higher co-occurrence of psychiatric disorders (P = 0.007) and less occurrence of alcohol dependence (P = 0.03). Conclusion: Findings underscore the need for heightened awareness, screening, and intervention efforts targeting pregabalin misuse within SUD treatment. Further research should focus on longitudinal studies to elucidate pregabalin dependence’s trajectory.