The goal of this study was to compare two surgical methods, the left carotid (LC) and the abdominal aorta (AA), for mouse instrumentation with telemetry devices, to determine the best method for measuring cardiovascular (CV) parameters by radiotelemetry in freely moving mice. Surgery success rate, postsurgical recovery rate, clinical parameters, CV data (baseline and response to nicotine) and circadian rhythm measurements were compared between these techniques. Brains of LC-implanted mice were evaluated for potential ischaemia by direct observation of the Circle of Willis anatomy and histopathology. For this purpose, a total of 31 CD-1 male mice were instrumented with PA C20 devices (10 with LC and 21 with AA). Mortality, morbidity, physical examination, body weight (BW), water and food consumption (W/FC), mean blood pressure (MBP) and heart rate (HR) were monitored daily during the recovery period (10 days). CV baseline data were recorded continuously during two periods of four days, and finally, both LC- and AA-implanted mice received an acute subcutaneous administration of 1 mg/kg nicotine; BP and HR were recorded during 5 h after nicotine administration. Results showed that, in LC-implanted mice, 80% survived surgery and recovered well. In contrast, only 57% of mice implanted with the AA technique survived surgery and some presented lethal complications. Both techniques had similar recovery times for BW and W/FC, comparable return to normal circadian rhythm (day 6 post-surgery) and similar CV baseline values. No significant differences were observed in CV response to nicotine between both groups of implanted CD-1 mice. No histopathological changes suggestive of ischaemia were noted in the brain of mice implanted in the LC. Six out of the eight LC-implanted mice remained in good health and had good pressure signal for at least 100 days post-surgery, while most of the AA-implanted mice lost the signal pressure within 14-49 days post-surgery. In conclusion, we believe that LC implantation in mice is superior to the AA technique and is more appropriate for long-term telemetry studies, especially for smaller (transgenic) animals.