Rationale, aims, and objectives: Management of pregnant women with sickle cell disease (SCD) represents a challenge to maternal healthcare services due to its potential complications with associated morbidity and mortality. Trustworthy evidence-based clinical practice guidelines (CPGs) have a major impact on supporting appropriate healthcare positive outcomes. The objective of this study was to critically appraise the quality of recent CPGs for SCD in pregnancy. Methods: We identified clinical questions and eligibility criteria, searched, and screened for CPGs using CPG databases, DynaMed, PubMed, and Google Scholar. Each included CPG was appraised by four independent appraisers using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE-II) instrument. An additional inter-rater analysis was conducted. Results: Four eligible CPGs were appraised: American College of Obstetricians and Gynecologists (ACOG); National Heart, Lung, and Blood Institute (NHLBI); National Institute of Health and Care Excellence (NICE); and Royal College of Obstetricians and Gynaecologists (RCOG). The AGREE-II standardized domain scores revealed variation between the quality of these CPGs. Overall, the recommendations were not significantly different between these four CPGs. Conclusions: In recent years, there has been an improvement in the reporting of CPG development methodology. CPG development working groups should aim to adhere to the AGREE II criteria to improve the standards and quality of CPGs. RCOG followed by NHLBI CPGs showed the highest quality and were strongly recommended. We recommend incorporating AGREE-II appraisal of CPGs in the education of obstetricians, gynecologists and hematologists to guide their selection of CPGs for their daily practice.