OBJECTIVES: Chronic low back pain (CLBP) with or without radiculopathy is a major expensive, and disabling condition around the globe. Limited safety and efficacy data of various analgesics make difficult in prescribing. Present study aimed at assessing the efficacy and safety of combination therapy of pregabalin and amitriptyline in patients with CLBP in Indian population. METHODS: A longitudinal prospective observational study was conducted at pain clinic of a public tertiary care hospital. Adult patients suffering from low back pain for >3 months, and who received pregabalin (75-150 mg/day) and amitriptyline (10/25 mg/day) were included in the study. Data collected for baseline and follow-ups of monthly through hospital visits and telephonic contacting until 6 months for VAS; baseline and 6 months for Modified Ostwery low back pain Disability questionnaire (MODQ). Percentage of patients achieved >50% of pain reduction by VAS score (0-100) after six months is the primary endpoint. Safety and improvement in quality of life after six months assessed as secondary endpoint. Analysis done by one way repeated measures anova. RESULTS: A total of 198 patients were included in this study with mean age of 44.8+12.4 years, 63% are having BMI >25kg/m, and duration of pain 30 (12-60) months. Magnetic imaging resonance findings have shown disc bulging (43.9%), disc herniation (12.6%), spondylosis (11.1%) and other problems. Significant reduction in pain was observed p<0.01 on VAS score after 6 months follow up. VAS&MODQ baseline median (IQR) scores found to be 75(60-90)&52(40-60), and after 6 months 35(20-50)&41(24-53), no improvement in quality of life found p=0.08. Dry mouth is being the commonest adverse event [in 80 (40.4)]. Other adverse events reported are headache, constipation, dizziness and postural hypotension.  CONCLUSIONS: Our results suggest that combination of pregabalin and amitriptyline are efficacious and safe in managing CLBP.