Background Urinary calculus illness is a prevalent clinical issue encountered by the medical community, particularly urologists, in contemporary society. Laser technologies have been widely accepted as standard modalities for lithotripsy applications. Using the Ho:YAG laser has expanded the range of applications for ureteroscopic stone management (URS), enabling the treatment of bigger stones in all regions of the upper urinary tract. It is noteworthy that ureteroscopy (URS) demonstrates superior rates of stone clearance for distal stones, regardless of their size, with a success rate of 94.5% compared to 74% for other treatment modalities. Significant variation exists in the reported results and problems associated with Ho:YAG laser lithotripsy across different trials, as documented in the literature. The procedure's outcome might vary based on factors such as the size of the stone, the length of impaction, the presence of ureteral damage and granulation, the kind and size of endoscopes used, and the specific energy settings employed by various operators. The present study aimed to evaluate the impact of Ho:YAG laser lithotripsy for ureteroscopic removal of proximal and distal ureter calculi. Methods This prospective observational study was carried out in the Department of Urology at DY Patil Medical College and Hospital, Pune, from March 2021 to March 2023. Patients diagnosed with a case of ureteric stone who opted for URSL during the study period were included. A total of 50 patients who underwent URSL in the urology department were included in this study. These were then grouped into those with proximal ureteral stones and distal ureteral stones. (25 each) Results The study observed that patients diagnosed with proximal ureteral stones had bigger calculi, with a mean stone size of 15mm, in comparison to patients with distal ureteral stones, with a mean stone size of 10mm (P=0.010). The stone burden was significantly higher for proximal ureteral stone patients than those with distal ureteric stones (P=0.010). The average duration of the operating procedure for upper ureter stones was 70 minutes, but for lower stones, the mean operative time was 45 minutes (P<0.001). No statistical significance was seen in the median age of patients between the two groups (P=0.89). The maximum number of cases in the upper stone group were in the age group of 16-30 years, and in the lower stone group was in the age group of 31-45 years. The prevalence of DJ stents at the time of presentation was higher among patients diagnosed with proximal ureteric stones than those with distal ureteric stones, with rates of 28% and 20%, respectively (P=0.508). Full fragmentation was successfully accomplished in all patients within the distal calculus group, accounting for 100% of the cases. At the same time, for proximal ureteric stones, a single laser lithotripsy session resulted in 92% (23 patients) achieving a stone-free status after two weeks. Conclusion The study observed that stone size, burden, and procedure duration were statistically significant among other criteria. Mean age, stone HU, prior DJ stent, and stone-free rate were statistically insignificant. The procedure indicated that Ho:YAG laser lithotripsy has efficacy in treating both proximal and distal ureteral stones, with minimal intraoperative and postoperative complications. None of the complications were due to laser energy.