Background This study evaluates the effectiveness of different maintenance strategies in preventing complications associated with removable partial dentures (RPDs). The aim is to assess how regular cleaning, professional check-ups, and overall denture care impact the longevity and functionality of RPDs while reducing common issues such as mucosal irritation, fractures, and bad breath. Methods A cross-sectional study was conducted at Bibi Aseefa Dental College, Larkana, from February 2023 to February 2024. A total of 120 patients using RPDs for at least six months were included. Data collection involved a structured questionnaire and clinical examination. Information on demographics, type of RPD, duration of use, maintenance habits, and reported complications was gathered. Chi-square and independent t-tests were applied for statistical analysis, with a significance level set at p < 0.05. Results Patients who followed regular cleaning routines and attended professional check-ups had significantly fewer complications than those who did not maintain their RPDs properly. Mucosal irritation, bad breath, and denture fractures were most prevalent among patients who neglected maintenance, with statistically significant differences observed across groups (p < 0.05). Flexible RPDs had a lower rate of fractures compared to acrylic-based RPDs. Socioeconomic status and education level also influenced maintenance habits, with higher-educated patients practicing better denture care. Conclusion Proper maintenance of RPDs plays a crucial role in preventing complications and enhancing prosthesis longevity. Regular cleaning, use of denture cleansers, and periodic dental check-ups significantly reduce issues such as irritation, staining, and structural damage. Improving patient education on RPD care and encouraging routine follow-ups can lead to better oral health outcomes and greater patient satisfaction.