Little is known about the challenges of routine renal replacement therapy in Sub-Saharan Africa. We investigated the fatal and nonfatal acute hemodialysis (HD) complications in patients with end-stage renal disease (ESRD) in two main dialysis centers in Cameroon. 1000 consecutive HD sessions incurred over a 4-month period by 129 patients (96 men, 74%) with ESRD, receiving two weekly HD sessions of 4 hours each, were considered. Personal and clinical profiles before, during, and within 24 hours after HD sessions were used to diagnose complications. Participants were aged 7 to 80 years (mean 46 years). In all, 452 acute complications were recorded in 411 (41%) of the 1000 HD sessions. Of the 11 types of complications, hypotension (25%), muscular cramps (22%), hypertensive crisis (14%), pruritus (10%), and fever (7%) were the most frequent. Three hundred and six complications (67.7%) occurred during understaffed nighttime. The vascular access was the main bleeding site with 64%. Being diabetic and ultrafiltration rate >1000 mL/h were associated with hypotension and muscle cramps. The shorter duration in dialysis was associated with the risk of bleeding and the disequilibrium syndrome while longer duration was associated with muscle cramps. Four deaths (three from bleeding and one from disequilibrium syndrome) occurred, all during nighttime. Nearly half of dialysis sessions in these settings are associated with acute complications, some of which are fatal. Those complications occurred mostly during understaffed periods. Urgent strategies are needed to quickly solve the human capital crisis in the health care sector.