Background. Frameless fixation with a thermoplastic mask is an alternative to traditional frame-based immobilization for Gamma-Knife stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). However, interruptions during beam-on time can significantly prolong treatment delivery, impacting patient experience and unit workflow. Aim. We investigated clinical and technical predictors of treatment interruptions, and the phases of treatment during which interruptions are most likely to occur. Methods. Patients undergoing frameless Gamma Knife SRS or FSRT in 2020 were retrospectively reviewed. Clinical parameters were extracted from electronic medical records. Dosimetric and treatment interruption data were obtained from Gamma Knife treatment reports. Univariate and multivariate analyses analyzed technical and clinical predictors of treatment interruptions. Results. Our cohort included 84 patients receiving 141 fractions encompassing 255 lesions. 49/84 (58.3%) were female, 79/84 (94.0%) had brain metastases, 49/84 (58.3%) were taking dexamethasone and 30/84 (35.7%) used analgesics. 89/106 (84.0%) courses were single fractions. Mean planned beam-on time was 37.1 minutes (range 7.1-118.8 min) versus a total bed time of 64.9 minutes (range 15-252min) per fraction. 64.5% (91/141) of fractions were interrupted at least once; 12/141 fractions were paused 20 times or more, with a maximum 54 pauses. The mean number of pauses per quartile decreased the further the patient proceeded in beam-on time, and patients receiving first lifetime cranial radiation paused more often than during subsequent fractions. At least one pause occurred in 100% of fractions with a planned beam-on time exceeding 60 minutes. Planned beam-on time, number of gating events and high-definition motion management alarms significantly correlated with total number of pauses on multivariate analysis (all p<0.0001); these three factors, along with prep time and number of operator-initiated pauses, predicted total time on the Gamma Knife couch (all p<0.0001). Clinical factors, medication use, and prior SRS/FSRT were not predictive of pauses. Conclusions. Planned beam-on time, number of gating events and high-definition motion management alarms significantly predicted likelihood of interruptions during frameless Gamma Knife SRS/FSRT. These factors should be considered in selection of immobilization method, especially if exceeding 60 minutes.