Purpose The aim of the study was to determine the feasibility of interstitial brachytherapy under non-anesthetist-administered moderate sedation, to identify factors influencing the insertion, and the total procedural time. Material and methods A total of 47 insertions with hybrid intracavitary and interstitial applicators were performed in 23 patients from March 2017 to March 2020. Moderate sedation was achieved with intravenous midazolam and fentanyl administered by non-anesthetist. Insertion time and procedural time was recorded. Univariate and multivariate analysis were performed to evaluate the impact of different factors on insertion and procedural time. Results A total of 238 needles (range, 2-8 per insertion) were implanted, with an average insertion depth of 30 mm (range, 20-40 mm). The mean doses for midazolam and fentanyl were 3 mg (standard deviation [SD] = 1) and 53.3 mcg (SD = 23.9) per insertion, respectively. The median insertion time was 30 minutes (interquartile range [IQR] = 22-40), and the median total procedural time was 4.3 hours (IQR = 3.6-5.2). First time insertion, insertions performed before 2019, and higher midazolam dose were associated with significantly longer insertion time, whereas longer insertion time, MRI-based planning, and insertions performed before 2019 were associated with significantly longer total procedural time. Conclusions Outpatient interstitial brachytherapy with non-anesthetist-administered sedation is achievable and well-tolerated. This method may significantly lessen the burden on hospital resources and has the potential to be cost-effective.