BACKGROUND: In unexplained infertility (UI), the use of intracytoplasmic sperm injection (ICSI) has been increased to prevent total fertilisation failure (TFF). However, there is little evidence to support improved clinical outcomes. AIM: The aim of the study was to assess whether ICSI improves the outcomes compared to conventional fertilisation (IVF) in UI. SETTINGS AND DESIGN: A retrospective cohort study in a tertiary centre. MATERIALS AND METHODS: Patients were divided into two groups. Group A in which ICSI-cycles were performed and Group B in which IVF-cycles were performed. All UI couples with females aged between 21 and 38 years who underwent the first long GnRH-agonist or GnRH-antagonist protocol stimulation cycle followed by fresh embryo transfer were included. UI couples who needed rescue-ICSI, donor-recipient cycles and pre-implantation genetic diagnosis were excluded. Outcomes were fertilisation rate, TFF, good-quality day 3 embryo, implantation rate, miscarriage rate and clinical pregnancy rate. STATISTICAL ANALYSIS USED: STATA 18.0 software (Stata Corp, TX, USA) was used. RESULTS: A total of 511 UI patients were included out of which 182 underwent ICSI and 310 underwent IVF cycles. Baseline characteristics were similar in both groups. The mean percentage fertilisation rate was comparable in the ICSI and IVF groups (67.18 ± 22.61 vs. 66.93 ± 26.66, = 0.92, respectively). TFF was lower in the ICSI group compared to the IVF group (2.7% vs. 5.8%, = 0.12). The mean number of good-quality embryo development rate on day 3 was similar between the ICSI and IVF groups ( = 0.93). Although implantation and clinical pregnancy rates were higher in the IVF group compared to the ICSI group with > 0.05, these differences were not statistically significant. CONCLUSION: The study reported reduced TFF in the ICSI group in comparison to the IVF group but was not statistically significant with comparable clinical outcomes.