Fibromyalgia (FM) is a chronic pain disorder characterized by widespread musculoskeletal pain, tender points and fatigue, secondary to altered pain perception and modulation system. Most of the patients also report muscle stiffness, sleep disorder, irritable bowel syndrome, and mood disorder. There is a lack of appropriate management of pain and associated emotional component. We report the beneficial effect of non-invasive, non-pharmacological and inexpensive management of pain and associated anxiety in FM by transcranial magnetic stimulation (TMS).Female FM patients (n=90) were recruited from our Rheumatology Clinic. Patients received TMS (0.5 Hz, 80% of motor threshold) at right dorso-lateral prefrontal cortex, in 8 sessions of 5 min at 5 min interval /day. The TMS sessions were repeated every day for 5d/week x 4 (TMS group), while controls (sham group) received only sham stimulation. Pre and post TMS at wk 0, 4 and 6, pain was assessed objectively by nociceptive flexion reflex (RIII reflex) from left biceps femoris muscle; the emotional component of pain by Beck Depression Inventory second edition (BDI-II) and the negative strategies for coping with pain by Coping Strategy Questionnaire (CSQ), while pain modulation by diffuse noxious inhibitory control. We also analyzed the potential role of single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) (rs4680) and 5-hydroxytryptamine (serotonin) 2A (5-HT2A) receptor (rs6313) genes on susceptibility to fibromyalgia. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the genotyping analyses. Genotype and allele frequencies were calculated and Chi square test was done for statistical analysis. Post-TMS (wk4), RIII threshold increased (p<0.01) in FM patients from 27.4±5.5V to 36.7±5.87V indicating analgesia, while it did not (p<0.62) change (28.6 ±6.04V to 29.1±5.5V) in sham group. The latency of RIII also increased (p<0.045) from 108.29 ±34.34 ms to 123.56±28.41 ms, post-TMS but not post-sham (112.37±28.65 to 109.78 ±30.21, p<0.84), while BDI-II score (12.46±3.21) at wk 0 which reduced (p<0.03) post-TMS to 7.45±1.87.The beneficial effect persisted till wk 6. : There were no significant differences in the frequencies of alleles and genotypes between patients and controls for the COMT and the 5-HT2A receptor gene polymorphisms (P > 0.05) in present case control study. Genetic polymorphisms T102C of 5HT2A gene and val158met of COMT gene have no association with fibromyalgia susceptibility. The study showed that repeated TMS in FM patients relieved pain, associated anxiety and depression as indicated by RIII reflex and BDI-II, respectively. We suggest that it may be a valuable and safe new therapeutic option for FM patients.