Background: Patient setup errors in External Beam Radiotherapy (EBRT) are minimized to a great extent, due to recent technological developments but in contrary brachytherapy received least attention in inter-fraction catheter movement and its impact in dose delivery. This article deals with inter-fraction interstitial catheter movement and its impact in dose delivery to the target. An attempt is made to study the dosimetric impact of this variation. Objectives: The objective of the study is to evaluate the inter-fraction variation in the position of implanted interstitial applicators and to assess the dosimetric impact in interstitial High Dose Rate (HDR) brachytherapy. Materials and Methods: 55 patients treated for carcinoma tongue, breast, buccal mucosa, cervix, floor of mouth and soft tissue sarcoma over a period of 2 years (December 2011-May 2013) were considered. All the patients underwent CT scan on the next day of the implant and 3D planning was done either by Eclipse or Oncentra Master plan Treatment Planning System (TPS). Patients were treated by HDR brachytherapy remote after-loading units, either by Gamma Med iX plus or Microselectron. At the end of the last fraction, CT scan was repeated and re-planning done. The variation in position of the implanted applicators/catheters and its impact on dosimetric parameters were evaluated and analyzed. Results: The range of positional displacement of the interstitial catheters ranges from 4.5 mm to 6.8 mm. The maximum variation in prescribed dose to D90 of Clinical Target Volume was 10.88%. Conclusions: If the total duration of interstitial implant of HDR brachytherapy extends for more than a week from the day of imaging, it is recommended to do CT imaging and re-plan again. It is mandatory to suture the buttons of the implant to the skin. Edema and movement of organs (e.g., tongue) are the main cause for the positional variation of the catheters.