CONTEXT Tetrahydro iso-α acids (THIAAs), derived from Humulus lupulus (hops), have demonstrated anti-inflammatory effects in vitro and in an animal model of rheumatoid arthritis (RA). Undenatured type 2 collagen has been found to be effective in clinical studies in RA and osteoarthritis (OA). OBJECTIVE The study intended to evaluate the efficacy and safety of a proprietary tablet containing 150 mg of n-enriched THIAA (nTHIAA) and 10 mg of undenatured type 2 collagen (UC-II) (containing 25% UC-II) in patients with arthritis. DESIGN The study was an open-label case series. This article also includes a case history for 1 participant. SETTING The study was conducted at the Functional Medicine Research Center (FMRC) in Gig Harbor, WA, USA, from February 2013-June 2013. PARTICIPANTS Participants were 17 adults, 12 women, and 5 men aged 39-69 y, who had chronic joint pain involving various joints, 13 with probable OA and 4 with possible RA. INTERVENTION Participants took 2 tablets of nTHIAA + UC-II 2 ×/d with meals for 12 wk. OUTCOME MEASURES Participants completed arthritis-related and quality-of-life questionnaires, at weeks 2, 4, 8, and 12: (1) the visual analog scale for pain (VAS-P); (2) the medical symptoms questionnaire (MSQ), with the analysis particularly focusing on the joint/muscle subscale and total scores; (3) the health and wellness outcome questionnaire (MOS-SF36), with the analysis particularly focusing on the physical and mental subscales; (4) the arthritis impact questionnaire (AIQ), with the analysis particularly focusing on the arthritis symptoms and daily living subscales; (5) the health assessment questionnaire (HAQ-DI) with the analysis particularly focusing on question 26 (Q26), which indicates overall pain during the week prior to the survey; and (6) the arthritis impact measurement scales 2 (AIMS2). At 12 wk, participants also completed the visual analog scale for efficacy (VAS-E). RESULTS All participants completed the 12-wk evaluation, and all reported improvements in pain. Significant improvements in scores on the questionnaires were observed as early as 2 wk. For example, the total score on the MSQ was significantly decreased from a mean of 20.76 ± 2.90 (SE) at baseline to 12.24 ± 2.81 after 2 wk (P < .001). At 12 wk, the participants rated the supplement's efficacy at 7.6 ± 0.6 of 10. At baseline, 13 of the 17 participants were using analgesics for joint pain, compared with only 4 participants at 12 wk. Two of those 4 had reduced their analgesic dosages. The studied supplement was well tolerated, and no serious side effects occurred. CONCLUSIONS The supplement containing nTHIAA and UC-II is safe and efficacious in participants with chronic joint pain.