OBJECTIVE: To compare the possible effects of wet-cupping therapy with conventional therapy on persistent nonspecific low back pain (PNSLBP). METHODS: In this randomized clinical trial, 180 participants with the mean age of 45±10 years old, who had been suffering from PNSLBP were randomly assigned to wet-cupping and conventional groups. The wet-cupping group was treated with two separate sessions (4 weeks in total) on the inter-scapular and sacrum area. In the conventional group, patients were conservatively treated using rest (6 weeks) and oral medications (3 weeks). The primary and the secondary outcome were the quantity of disability using Oswestry Disability Index (ODI), and pain intensity using Visual Analogue Scale (VAS), respectively. RESULTS: There was no significant difference in demographic characteristics (age, gender, and body mass index) between the two groups (P>0.05). Therapeutic effect of wet-cupping therapy was comparable to conventional treatment in the 1st month follow-up visits (P<0.05). The functional outcomes of wet-cupping at the 3rd and 6th month visits were significantly increased compared to the conventional group. Final ODI scores in the wet-cupping and conventional groups were 16.7 ± 5.7 and 22.3 ± 4.5, respectively (P<0.01). CONCLUSION Wet-cupping may be a proper method to decrease PNSLBP without any conventional treatment. The therapeutic effects of wet-cupping can be longer lasting than conventional therapy. (Registration No. IRCT2013021672741)).