Integrase strand transfer inhibitors (INSTIs) are the preferred first-line anchor drug for antiretroviral therapy globally. However, post-marketing authorisation studies continue to find previously unidentified adverse events (AEs) associated with INSTIs. A pharmacovigilance study was conducted to investigate AEs associated with INSTIs submitted to the Botswana national pharmacovigilance database (BoMRA). All suspected AE reports in which INSTIs were identified as the primary suspect were included for analysis. Descriptive analysis was used to characterise the AEs, and disproportionality analysis was used for signal detection. Causality assessment was conducted using the World Health Organization-Uppsala Monitoring Centre system, the Liverpool ADR Causality Assessment Tool, and the Naranjo Causality Assessment algorithm. Agreement between the methods was assessed through the Cohen's Kappa ({kappa}) test. A total of n = 112 AE reports were reported for cabotegravir and dolutegravir as the primary suspect drugs. Most reports involved females and adults, while dolutegravir was associated with the majority (78.6%). Skin and subcutaneous AEs (25.0%) and rash (10.7%) were the most frequently reported AEs at the system organ class (SOC) and reported preferred term (PT) levels, respectively. Reporter qualification influenced report completeness, with nurses submitting reports with the highest median completeness score. Most reported AEs were consistent with the established safety profiles of cabotegravir and dolutegravir. However, the study identified unlabelled AEs for both cabotegravir and dolutegravir, including decreased libido, hallucination, severe obesity, acquired lipodystrophy, gynecomastia, cheilitis, and hyperpigmentation. These are potential safety signals that warrant further investigation and underscore the importance of national pharmacovigilance data for ongoing post-marketing safety surveillance and for generating local safety data insights.