Chagas disease (CD) and tuberculosis (TB) are important health problems in Bolivia. Current treatments for both infections require a long period of time, and adverse drug reactions (ADRs) are frequent. This study aims to strengthen the Bolivian pharmacovigilance system, focusing on CD and TB. A situation analysis of pharmacovigilance in the Department of Cochabamba was performed. The use of a new local case report form (CRF) was implemented, together with the CRF established by the Unidad de Medicamentos y Tecnología en Salud (UNIMED), in several healthcare centers. Training and follow-up on drug safety monitoring and ADR reporting was provided to all health professionals involved in CD and TB treatment. A comparative analysis of the reported ADRs using the CRF provided by UNIMED, the new CRF proposal, and medical records, was also performed. Our results showed that out of all patients starting treatment for CD, 37.9% suffered ADRs according to the medical records, and 25.3% of them were classified as moderate/severe (MS). Only 47.4% of MS ADRs were reported to UNIMED. Regarding TB treatment, 9.9% of all patients suffered ADRs, 44% of them were classified as MS, and 75% of MS ADRs were reported to UNIMED. These findings show that the reinforcement of the Bolivian pharmacovigilance system is an ambitious project that should involve a long-term perspective and the engagement of national health workers and other stakeholders at all levels. Continuity and perseverance are essential to achieve a solid ADR reporting system, improving patient safety, drug efficacy and adherence to treatment.