Abstract Objective In 2011, the government of Cameroon launched its performance‐based financing (PBF) scheme. Our study examined the effects of the PBF intervention on the availability of essential medicines (EM). Methods Randomised control trial whereby PBF and three distinct comparison groups were randomised in a total of 205 health facilities across three regions. Baseline data were collected between March and May 2012 and endline data 36 months later. We defined availability of multiple EM groups by assessing stock‐outs for at least one day over the 30 days prior to the survey date and estimated changes attributable to PBF using a series of difference‐in‐difference regression models, adjusted for relevant facility‐level covariates. Data were analysed stratified by region and area to assess effect heterogeneity. Results Our estimates suggest that PBF intervention had no effect on the stock‐outs of antenatal care drugs ( P = 0.160), vaccines ( P = 0.396), integrated management of childhood illness drugs ( P = 0.681) and labour and delivery drugs ( P = 0.589). However, the intervention was associated with a significant reduction of 34% in stock‐outs of family planning medicines ( P = 0.028). We observed effect heterogeneity across regions and areas, with significant decreases in stock‐outs of family planning products in North‐West region ( P = 0.065) and in rural areas ( P = 0.043). Conclusions The PBF intervention in Cameroon had limited effects on the reduction of EMs stock‐outs. These poor results were likely the consequence of partial implementation failure, ranging from disruption and discontinuation of services to limited facility autonomy in managing decision‐making and considerable delay in performance payment.