Background <p>Renin–angiotensin system inhibitors (RASis), including ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs), are commonly initiated in primary care for various clinical indications. However, the risk of hyperkalaemia and increased serum creatinine levels after initiation has not been well studied in Asian populations.</p> Methods <p>We conducted a retrospective cohort study of all patients aged 18 years and older who initiated RASi treatment at National University Polyclinics, a network of seven primary care clinics in Singapore, between 28 September 2020 and 31 June 2024. The study outcomes were the incidence of hyperkalaemia and elevated serum creatinine levels after RASi initiation. Multivariable regression was used to evaluate the covariates associated with these outcomes.</p> Results <p>The cohort comprised 9,926 patients whose baseline creatinine and post-initiation creatinine or potassium data were available. Within our cohort, 181 patients (1.8%) had hyperkalaemia, comprising 149 (1.5%) mild cases, 28 (0.3%) moderate cases and 4 (&lt; 0.1%) severe cases; 249 (2.5%) patients had a major elevation in serum creatinine of 30% or more from baseline. Risk factors for hyperkalaemia include age, Indian or ‘Other’ ethnicity, increased baseline serum creatinine and increased baseline serum potassium. For major serum creatinine elevation, risk factors included ‘Other’ ethnicity, comorbid diabetes mellitus and concomitant diuretic use.</p> Conclusion <p>Hyperkalaemia and major serum creatinine elevation are uncommon adverse events following RASi initiation.</p>