Managing mares through unpredictable behaviors associated with fluctuating hormones is frustrating, particularly during performance. A variety of solutions have been explored, but without reliable success. The synthetic progestin altrenogest, marketed for estrus suppression in the mare, is the current industry paradigm. Commonly administered orally or sustained release injectable formulations, both pose risks, leading to poor owner compliance. We investigated the ability of a novel biomedical device to deliver altrenogest through the vaginal mucosa directly compared with conventional oral administration. In total, 12 grade mares were utilized for this study during the physiologic breeding season. Mares were enrolled within a treatment group spanning three estrous cycles in a crossover design. Intravaginal ring altrenogest (IVRA), oral altrenogest (OA) and a control placebo vaginal ring (IVRP). Group IVRA: 14.2cm diameter silicone ring containing 1% powder altrenogest placed into the cranial vaginal vault day 5 of diestrus (0d = ovulation). Group OA: administered commercially available altrenogest (Regu-Mate®, Merck & Co., Inc., Rahway, NJ) orally daily at 0.044 mg/kg. Group IVRP: insertion of a silicone vaginal ring without altrenogest into the vaginal vault. Blood was collected at each trial initiation (T0) and at 2h, 24h, 72h, 10 days and plasma stored at -80°C until pharmacokinetic (PK) evaluation utilizing modern liquid chromatography tandem mass spectrometry(LC/MS/MS). Blood samples were also collected (days 5, 11, 15, 22) to determine native progesterone levels. Transrectal ultrasonographic evaluation was performed every five days following ovulation. Controlled exposure to a stallion occurred every other day. Values are given as mean ± standard error of mean. IVRA peak plasma levels: 1.45 ng/ml following ring insertion; average steady state level: 0.3 ng/ml. OA peak plasma levels: 1.8 ng/ml following administration; average steady state: 0.55 ng/ml. IVRP: no altrenogest detected. Cmax for IVRA and OA groups was reached within 2 hours. IVRA eliminated peaks/troughs identified in group OA, demonstrating a steady state. Transrectal ultrasonography revealed group IVRA maintained a CL an average of 20.8 ± 1.3, group OA for 21.4 ± 0.75 and IVRP for 14.4 ± 1.2 days. There was no difference in native progesterone levels amongst groups. Groups IVRA and OA maintained significantly longer luteal phases than IVRP (p<0.0001 and p<0.002, respectively). Mares in group IVRA displayed significantly lower teasing scores than IVRP (p<0.009). Groups IVRA and OA were not significantly different (p<0.188). Previous studies determined therapeutic levels of altrenogest at or above 0.5 ng/ml but our observations with mare behavior and PK data suggest efficacy at lower limits of quantification (0.1 ng/ml). An equine intravaginal ring represents a novel medical device for effective delivery of therapeutics and future applications.