This paper presents an analysis of tram safety in Switzerland and best practices for operating trams in mixed traffic developed by Swiss tram operators and authorities. Operating trams in mixed traffic can create safety problems because trams have differing operating characteristics from other roadway traffic. It is not always feasible to provide complete separation of tramways from other road users in crowded cities. Therefore, improving tram safety in mixed traffic has gained significant attention in recent years. In Switzerland, the majority of tram collisions occur with cars, but the most severe consequences stem from collisions with pedestrians and bicycles. The location of tram collisions is linked to the likelihood of interactions and, therefore, to the amount of tram service and traffic levels. Unfortunately, the possibilities for quantitatively assessing the safety of specific street configurations are limited because of missing secondary data on context, the small number of tram accidents, and the large number of potentially important variables. Therefore, this research supplemented available quantitative data with qualitative data. The most pertinent safety issues operators face are conflicts with turning vehicles (left-turn issue), disrespect of traffic signals, confusing or ambiguous layouts, distracted pedestrians, pedestrians unaware that trams have priority, missing physical separation in semiexclusive running sections, and lack of visibility. Although many measures have been successfully applied to mitigate these issues, it is not possible to achieve absolute safety, particularly where people’s behavior is a main source of accidents.