|Abstract Background Twice-weekly maintenance hemodialysis sessions in patients with end stage renal disease are commonly practiced due to economic constraints in developing countries including Eritrea. To ameliorate the paucity of data on the subject, our study aims to shed light on the patterns of intradialytic complications exclusively in patients undergoing twice-weekly hemodialysis in the country. Methods A descriptive cross-sectional study was conducted from March 01 to July 31, 2018 at Dialysis Unit of Orotta National Referral Hospital, Asmara, Eritrea in patients with end stage renal disease undergoing twice-weekly hemodialysis. Hemodialysis sessions were assessed for intradialytic complications. Data were fed into and analyzed using Epi-Info and Microsoft Excel. Results A total of 29 patients were included in the five-month study period. Males were 19 (65.5%) and females were 10 (34.5%). More than half of the patients had diabetes. Out of the total 573 hemodialysis sessions, 176 (30.7%) of them involved one or more intradialytic complication. Hypotension was the most common complication occurring in 10% of the sessions followed by nausea and vomiting (5.24%), hypertension (5.06%), muscle cramps (4.71%), and headache (4.54%). Other complications such as back pain, chest pain, fever, chills and itching occurred in less than 3% of the sessions. There was no death immediately associated with the complications. Half of the intradialytic complications occurred in patients with diabetes. There was a positive correlation between intradialytic hypotension and diabetes, ultrafiltration volume as well as eating during hemodialysis. Use of central line catheter as a vascular access was associated with higher complication rate. Conclusion Twice-weekly hemodialysis for end stage renal disease patients probably has similar intradialytic complications as the “standard” thrice-weekly frequency. Although twice-weekly hemodialysis schedule is certainly unsuitable for some patients, its advantage of preserving residual kidney function can prevent excessive interdialytic weight gain and thus lowering the risk of intradialytic hypotension related with higher ultrafiltration rate. Being the first study in the country on dialysis complications, we recommend further large scale research in the future.