OBJECTIVE: Many of the "antiseptic" practices recommended by health care professionals for insulin injection have been successfully challenged as unnecessary. Since people with diabetes have long been observed to inject their insulin through their clothing, this study was undertaken to determine the safety and perceived benefits of administering insulin by this "rogue" technique. RESEARCH DESIGN AND METHODS: Fifty people with insulin-treated diabetes were randomized into a 20-week single-blinded prospective crossover study comparing the conventional subcutaneous injection technique (with skin preparation) to an experimental injection technique through clothing. Skin assessment, glycated hemoglobin levels, and leukocyte count were determined before randomization, at 10 weeks (before crossover), and again at 20 weeks (at completion). The participants injected through a single layer of fabric, which ranged from nylon to denim. Problems, benefits, type of clothing, and other comments were recorded by the subjects in an injection log. RESULTS: Forty-two (84%) subjects completed the study. The mean age was 41 years (range, 23-63 years), 50% were women, 86% were Caucasian, and 80% had type I diabetes. The mean duration of diabetes was 14 years (range, 1-33 years). Fifty-one percent had > 16 years of education. The demographic characteristics of the dropouts were similar to those who completed the study. Over the 20-week period approximately 13,720 injections were performed by participants. None of the subjects experienced erythema, induration, or abscess at injection sites. Neither the glycated hemoglobin levels nor the leukocyte counts differed between the conventional and experimental regimens. During the injection-through-clothing phase of the study, only minor problems, such as blood stains on clothing and bruising, were recorded in the logbooks. However, subjects reported that injection through clothing offered benefits such as convenience and saving time. CONCLUSIONS: It is safe and convenient to inject insulin through clothing.