Background: Transseptal puncture (TSP) remains a demanding procedural step in access-ing the left atrium with inherent risks and safety concerns, mostly related to cardiac tamponade.Objective: Based on our own experience with 249 TSP procedures and in-depth literature review, we present our results and offer several tips and tricks that may render TSP successful and safe.Methods: This prospective study comprised 249 consecutive patients (146 men), aged 41.6+17.4 years, undergoing TSP by a single operator for ablation of a variety of arrhythmias, mostly related to left accessory pathways (n=145) or left atrial tachycardias (n=33) and more recently, atrial fibrillation (n=70). TSP was guided by fluoroscopy alone in all patients without the use of echocardiography im-aging. In addition, an extensive literature review of TSP-related topics was carried out in PubMed, Scopus and Google Scholar.Results: Among 249 patients, 33 patients were children or young adolescents (aged 7-18 years); 14 patients were undergoing a repeat procedure. Patients with a manifest accessory pathway were the youngest (mean age 33.7+15.9) and patients with atrial fibrillation the oldest (mean age 56.0+10.8 years). A successful TSP was accomplished in 247 patients (99.2%). Two (0.8%) procedures were complicated by cardiac tamponade managed successfully with pericardiocentesis or surgical drainage. Review of the literature revealed no systematic reviews and meta-analyses of TSP studies; however, several patient series have documented that fluoroscopy-guided TSP, with various modifications in the technique employed in the present series, have been effective in 95-100% of the cases with a complication rate ranging from 0.0% to 6.7%, albeit with a mortality rate of 0.018%-0.2%. Echo im-aging techniques were employed in cases with difficult TSP.Conclusion: Employing a standardized protocol with use of fluoroscopy alone minimized serious complications to 0.8% (2 patients) among 249 consecutive patients undergoing TSP for ablation of a variety of cardiac arrhythmias. Based on this single-operator experience and review of the literature, a list of practical tips and tricks is provided for a successful and safe procedure, reserving the more ex-pensive and patient inconveniencing echo-imaging techniques for difficult or failed cases.