The most harmful Dosha can vary depending on individual circumstances, but Kaal Sarp Dosha and Pitra Dosha are often considered particularly challenging. These Doshas are believed to bring significant obstacles, misfortune, and disruptions in various aspects of life, such as health, relationships, and career. However, the impact of any Dosha depends on the overall alignment of planets in your birth chart, and an experienced astrologer can provide guidance on which Dosha may be most detrimental in your specific case.