OBJECTIVE: To compare economic value of two administration methods (self-injection and ambulatory care) of anti-rheumatoid biologics (etanercept) by application of cost-effectiveness analysis (CEA). METHODS: From A societal perspective, we gathered cost data and outcome data. Cost data: 1) direct medical cost: physician visit fee, injection fee, laboratory test fee, and in-house self-injection guidance fee (from health insurance fee schedule), drug costs (hypothetical costs - since etanercept is not approved by Ministry of Health, Labour and Welfare yet); 2) direct non-medical cost: transportation cost. Data were gained from "Rheumatoid tomonokai", RA patients organization in Japan and teaching cost of self-injection. To estimate teaching cost, we conducted a survey to health care provider; AND 3) indirect cost: productivity loss. Outcome data: ACR20 gained from 3rd phase of clinical trial data of etanercept in the Japan and safety issues subject to self-injection, such as delayed finding ADR, accidentally impale needles to other people, and so on. Such data were gained from case report form (CRF). Because we set the time horizon for analysis as 1 year, we did not apply discount rate. We performed sensitivity analyses on 1) incidence of ADR; 2) education cost; 3) frequency of hospital visit; AND 4) productivity loss. RESULT: Effectiveness of self-injection care and ambulatory care were considered to be similar. Adverse reaction due to self-injection was not reported. Thus, we conducted cost minimization analysis. Total cost of self-injection group including indirect costs was JPY2,674,758 ($US22,746), which was lower than that of ambulatory care group, JPY3,255,110 ($US27,682). CONCLUSION: As far as effectiveness, ambulatory care are the same. Self-injection therapy is preferable, especially including indirect costs.