Abstract Introduction Hypoactive Sexual Desire Dysfunction (HSDD) in women is of multifactorial etiology with the best possible response on identifying modifiable factors and addressing them. With sexual boredom being one such factor in women with HSDD in a monogamous heterosexual relationship, the factors that improve boredom are expected to improve sexual desire in these women. Objective To evaluate sexual novelty as a therapeutic strategy to treat HSDD in women in monogamous heterosexual relationships using a prospective randomized study design. Methods The study was initiated following institutional review board approval. The participants, who expressed sexual boredom during our initial survey on sexual boredom in women in monogamous heterosexual relationships, female outpatients (in monogamous heterosexual relationships) with non-sexual complaints, and female partners of male patients with non-sexual complaints who agreed to participate in the study voluntarily were included. The exclusion was based on an evaluation of the participants by qualified medical specialists who diagnosed sexual, psychological, medical as well as gynecological conditions affecting sexual desire. Included participants attributing reduced sexual desire to sexual boredom on initial screening with Decreased Sexual Desire Screener (DSDS) were administered the Sexual Boredom Scale (SBS), to record the degree of sexual boredom in these women at the time of entry into the study. The participants were divided into two groups based on the computer-generated random numbers. The participants in group A received psychotherapy (included behavior therapy and/or cognitive behavior therapy and/or mindfulness) alone and group B received psychotherapy and a sexual novelty package (included any novelty related to sexuality other than trying a new sexual partner) as their planned intervention for a period of 6 months. The participants in both groups were administered the Elements of Desire Questionnaire (EDQ) at the beginning and at the end of the study to assess their sexual desire status. Mean and standard deviation was calculated for categorical variables, namely, age, period of monogamy, SBS score, and EDQ scores. The linear and multiple regression analysis was done to assess the effect of the age of the participant, and period of monogamy on boredom, and to know any influence of age, period of monogamy, and boredom level on the degree of improvement in sexual desire following treatment. A p-value of ≤ 0.05 was considered statistically significant. Results The study was conducted from January 2019 to May 2023 with a sample size of 398. There was no statistically significant difference between the groups as far as the age (36.5±10.8 years Vs 36.4±10.7 years), period of monogamy (10.9±7.7 years Vs 11.7.9±8.5 years), SBS score (71.8±30.8 Vs 73.1±43.9), and baseline EDQ score (1.5±0.6 Vs 1.4±0.6) were concerned. However, post-intervention, the sexual novelty group showed better improvement in EDQ score, which was statistically significant. The lower age of the participant and a longer period of monogamy were seen to impact sexual desire adversely on the multiple regression model. Conclusions Sexual novelty as a novel therapeutic strategy was successful in treating our study participants attributing reduced sexual desire to sexual boredom while being in a monogamous heterosexual relationship. Disclosure No.