Zeno, a new handheld device, produces low-level heat (controlled to 46.5–49.0°C) that may be applied to acne vulgaris lesions via a small metal tip. The purpose of this study was to evaluate the efficacy and safety of Zeno when it was used at a treatment time 20% lower than in an earlier study. Our study was conducted at 2 clinical sites with a total of 15 subjects and was randomized and controlled within a single subject. Eligible subjects had 2 similar acne lesions on the face. One lesion was treated with Zeno and the other with a placebo device; both lesions were treated twice on the first day and once on the second day. Follow-up assessments were made immediately before the second treatment (typically 4 hours after the first treatment) and the third treatment (typically 24 hours after the first treatment) and on day 5. The primary end point was the time to resolution of treated acne lesions. Secondary end points, including investigator and subject assessments on a blemish-change assessment scale, were evaluated. Any adverse events were reported. One subject failed to appear for appointments and was lost to follow-up and not included in the analysis. In 7 of the remaining 14 subjects, lesions improved or resolved sooner with Zeno than with placebo. In 3 subjects, improvement or resolution times were the same; in the 4 remaining subjects, placebo-treated lesions improved earlier. Adverse events were not observed with each device in the 14 subjects. Zeno appears to be an effective, safe take-home device for use alone or as adjunctive therapy with prescribed medications. There may be a link between dosage and efficacy.